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Sample records for acting neuromuscular blocking

  1. [Monitoring of neuromuscular blocking].

    PubMed

    Chamorro, C; Silva, J A

    2008-02-01

    Neuromuscular blockade monitoring aims should be based on effectiveness criteria, that is, to administer the lowest effective dose, and on security criteria, avoiding overdosage and detecting possible residual blockade before patient extubation. A neuromuscular blockade monitoring and usage protocol should be available with predefined objectives for each patient to achieve the minimum effective doses. Maintenance of a light blockade level probably influences the decrease in complications associated with these drugs' use. Train-of-four monitoring, along with muscular movement detection allow adjustment to meet these aims. Ulnar nerve stimulation with response detection in the adductor pollicis muscle is the recommended neurostimulation in critically ill patients, while facial neurostimulation is recommended in situations where edema or skin temperature prevent correct ulnar nerve stimulation. Ensuring adequate sedation and analgesia in a paralysed patient is essential. An inadequately sedated but paralysed patient may subsequently suffer serious psychological and emotional stress. Bispectral index monitoring with sedative doses adjusted to 40-60 values assures, in most situations, correct sedation. PMID:18405539

  2. Steroidal Ammonium Compounds as New Neuromuscular Blocking Agents.

    PubMed

    Rao, Zhigang; Hu, Hao; Tang, Jiazhi; Liu, Zhiying; Yang, Yue; Qiu, Guofu; Xiao, Yuling; Liu, Peng; Hu, Xianming; Zhou, Xiaoju; Hong, Xuechuan

    2016-05-01

    Neuromuscular blocking agents are widely used as an anesthesia auxiliary in surgery, which induce relaxation of skeletal muscles by blocking signal transmission at the neuromuscular junction. Many neuromuscular blocking agents s were developed over the past decades, but none of them fully meets the needs of the clinic by various reasons. In this study, a series of quaternary ammonium steroidal neuromuscular blocking agents were synthesized and evaluated on isolated mouse phrenic nerve-hemidiaphragms for their bioactivities. The initial separation of mono- and bis-quaternary ammonium compounds turned out to be very challenging on regular silica gel chromatography. Therefore, a facile purification method, in which the silica gel was pretreated with methanolic sodium bromide solution, was finally achieved. Compounds 3g (0.36 μm) and 4g (0.37 μm) exhibited excellent neuromuscular blocking activities, which were about sixfold to sevenfold higher in potency than that of rocuronium (2.50 μm). In addition, other bis-quaternized compounds also showed good potencies close to that of rocuronium. Furthermore, the preliminary structure-activity relationship of this series was also elucidated. Benzyl group was found to be a promising quaternary group in this series. PMID:26684806

  3. Synthesis and structure-activity relationships of neuromuscular blocking agents.

    PubMed

    Tuba, Zoltan; Maho, Sandor; Vizi, E Sylvester

    2002-08-01

    The first use of neuromuscular blocking agents (muscle relaxants) in clinical practice (1942) revolutionised the practice of anaesthesia and started the modern era of surgery. Since 1942 introduction of tubocurarine (18) neuromuscular blocking agents have been used routinely to provide skeletal muscle relaxation during surgical procedures allowing access to body cavities without hindrance from voluntary or reflex muscle movement. After the introduction of tubocurarine and the depolarizing suxamethonium chloride (4) (1949) several nondepolarizing steroidal and nonsteroidal neuromuscular blocking agents with different onset time and duration of effect were introduced e.g. gallamine triethiodide (1) (1949), methocurine (2) (1949), alcuronium chloride (3) (1963), pancuronium bromide (9) (1968), vecuronium bromide (11) (1982), pipecuronium bromide (10) (1982), atracurium besylate (5) (1982), doxacurium chloride (6) (1991), mivacurium chloride (8) (1992), rocuronium bromide (12) (1994) cisatracurium besylate (7) (1996), and rapacuronium bromide (13) (2000). SZ 1677 (14) a steroid type nondepolarizing neuromuscular blocking agent under development (preclinical phase). This review article deals with a comprehensive survey of the progress in chemical, pharmacological and, in some respects, of clinical studies of neuromuscular blocking agents used in the clinical practice and under development, including the synthesis, structure elucidation, pharmacological actions, structure activity relationships studies of steroidal and nonsteroidal derivatives. PMID:12171561

  4. Neuromuscular block after intra-arterially injected acetylcholine

    PubMed Central

    Pinelli, P.; Tonali, P.; Gambi, D.

    1973-01-01

    It has been suggested that the effect of ACTH in myasthenia gravis may be ascribed to an action involving neuromuscular transmission which favours repolarization processes, with a tendency towards hyperpolarization of the membranes of muscle fibres and motor nerve endings. A similar mechanism has been postulated for the action of ACTH in epilepsy (Klein, 1970). A direct or indirect action on nerve membrane would interfere with depolarization. There is evidence of raised concentration of intracellular potassium and increased outflow of sodium ions which would cause hyperpolarization of the membrane. This paper studies the effect of ACTH on the late block of neuromuscular transmission caused by acetylcholine (ACTH). Images PMID:4350704

  5. Neuromuscular block after intra-arterially injected acetylcholine

    PubMed Central

    Tonali, P.; Gambi, D.

    1973-01-01

    The neuromuscular depolarizing block induced by intra-arterially injected ACh was studied to determine the variability in the same subject and in different subjects without disorders at the motor end-plate. Amplitude of action potentials of the opponens pollicis muscle evoked by intermittent repetitive supramaximal stimulation of the median nerve at the wrist were recorded for one hour from the beginning of ACh injection. The features of prompt and late depression stages after the injection were analysed statistically. Re-testing of the same subjects after a while shows that, in spite of all efforts to maintain the same experimental conditions, variations do occur in late depression. Time course and duration are particularly affected, while the degree of depression is altered but slightly. The presence of such variations limits this test to evaluation of the influence of other factors only within their already established statistical limits. Images PMID:4350703

  6. Solid state characterization of an neuromuscular blocking agent--GW280430A.

    PubMed

    Zhu, Haijian Jim; Sacchetti, Mark

    2002-03-01

    GW280430A is an ultrashort-acting neuromuscular blocking agent and is targeted for muscle relaxation as part of the intubation surgical procedure. The objective of this work was to perform solid state characterization on GW280430A and to evaluate the relationship between water content and glass transition temperature (Tg). GW280430A was characterized by differential scanning calorimetry, thermogravimetric analysis, powder X-ray diffraction (PXRD), microscopy and moisture sorption. The effect of water content on the Tg of GW280430A was evaluated by equilibrating the material over saturated salt solutions at a range of relative humidities (6.4-72.6%) and determining the Tg by DSC using hermetically sealed aluminum pans. GW280430A undergoes dehydration at 40 degrees C, glass transition at 130 degrees C and decomposition at 190 degrees C by differential scanning calorimetry. By PXRD and moisture sorption, GW280430A is an amorphous material and deliquesces at about 70% RH at room temperature. Water acts as a potent plasticizer for GW280430A and the Tg decreases significantly as the water content increases. No measurable decomposition of GW280430A was observed after 4 weeks at 40 degrees C/75% RH. PMID:11839434

  7. Comparison of mechanomyography and acceleromyography for the assessment of rocuronium induced neuromuscular block in myotonic dystrophy type 1.

    PubMed

    Vanlinthout, L E H; Booij, L H D J; van Egmond, J; Robertson, E N

    2010-06-01

    We measured acceleromyography and mechanomyography simultaneously with monitoring of rocuronium-induced neuromuscular block in four patients with myotonic dystrophy type 1. Furthermore, we compared neuromuscular block measures from these patients with those from normal controls from previous studies. In myotonic dystrophy type 1 patients, the dose-response curve obtained with acceleromyography was steeper and right-shifted compared with that obtained using mechanomyography. However, the effective doses to produce 95% neuromuscular block determined with both acceleromyography and mechanomyography were similar to each other and to values found in normal patients. In the three myotonic dystrophy type 1 patients with mild to moderate disease, times to recovery from block were similar to those observed in normal controls. In both patients and normal controls, neuromuscular block recovered faster with acceleromyography. However, in one patient with severe muscle wasting, recovery of neuromuscular block was prolonged. We conclude that mechanomyography and acceleromyography cannot be used interchangeably to monitor neuromuscular block in myotonic dystrophy type 1 patients. PMID:20565393

  8. Preferences of Mexican anesthesiologists for vecuronium, rocuronium, or other neuromuscular blocking agents: a survey

    PubMed Central

    Nava-Ocampo, A A; Ramírez-Mora, J C; Moyao-García, D; Garduño-Espinosa, J; Salmerón, J

    2002-01-01

    Background Several neuromuscular blocking (NMB) agents are available for clinical use in anesthesia. The present study was performed in order to identify preferences and behaviors of anesthesiologists for using vecuronium, rocuronium or other NMB agents in their clinical practice. Material and methods The cross-sectional survey was applied at the Updated Course of the Colegio Mexicano de Anestesiología performed last year. Of 989, 282 (28.5%) surveys were returned. Results Most anesthesiologists were working at both public and private hospitals, performed anesthetic procedures for hospitalized and ambulatory patients, and anesthetized children as well as adults. Respondents did not consider mechanomyography as the gold standard method for neuromuscular monitoring. The T25 was not recognized as a pharmacodynamic parameter that represents the clinical duration of the neuromuscular block. Most answered that vecuronium induces less histamine release than rocuronium, had never used any neuromuscular monitor, did not know the cost of vecuronium and rocuronium, and preferred rocuronium in multiple-sampling vials and vecuronium in either a vial for single or multiple sampling. Rocuronium was preferred for emergency surgery in patients with full stomach only. Almost all of anesthesiologists that conserve the unused drug did it without refrigeration and more than 30% conserve the unused drug in one syringe for further use. Conclusion Vecuronium was preferred for most clinical situations, and the decision for this choice was not based on costs. Storage of unused drugs without refrigeration in a single syringe for purpose of future use in several patients represented a dangerous common practice. PMID:11991809

  9. Magnesium-induced recurarisation after reversal of rocuronium-induced neuromuscular block with sugammadex.

    PubMed

    Unterbuchner, C; Ziegleder, R; Graf, B; Metterlein, T

    2015-04-01

    A 61-year-old woman (57 kg, 171 cm) underwent surgery under general anaesthesia with desflurane 5.8-6.1 vol. % end-tidal, remifentanil 0.2-0.4 μg/kg/min and rocuronium 35 mg (0.61 mg/kg). On return of the second twitch in the train-of-four (TOF) stimulation measured by acceleromyography, sugammadex 120 mg (2.1 mg/kg) was given. After complete neuromuscular recovery, magnesium sulphate 3600 mg (60 mg/kg) was injected intravenously over 5 min to treat atrial fibrillation. This was associated with recurarisation with a nadir [first twitch=25%, TOF ratio (TOFR)=67%] 7 min after the start of the magnesium sulphate infusion (magnesium plasma level: 2.67 mM). A spontaneous twitch value and a TOFR of >90% were observed 45 min after the beginning of the magnesium sulphate infusion under general anaesthesia. Rapid infusion of magnesium sulphate may re-establish a sugammadex-reversed, rocuronium-induced neuromuscular block during general anaesthesia, probably because of the high plasma level of magnesium (2.67 mM). Desflurane and a small fraction of unbound rocuronium may amplify the known muscle relaxing effects of magnesium. Intravenous injection of magnesium sulphate is not recommended in patients after general anaesthesia with neuromuscular relaxants, particularly after sugammadex reversal. Quantitative neuromuscular monitoring should be used for reversing aminosteroid muscle relaxants with sugammadex--particularly in combination with magnesium injection--to prevent post-operative residual curarisation. PMID:25582520

  10. [Reversal of rocuronium induced neuromuscular block with sugammadex in a patient with myasthenia gravis].

    PubMed

    Nakamori, Erisa; Nitahara, Keiichi; Sugi, Yasuyuki; Katori, Kiyoshi; Matsuzaki, Akiko; Higa, Kazuo

    2013-08-01

    We report a patient with myasthenia gravis whose rocuronium induced neuromuscular block was reversed with sugammadex. A 26-year-old man, 175 cm and 76 kg, with myasthenia gravis, was scheduled for extended thymectomy under general anesthesia. An epidural catheter was inserted at the T5-6 interspace before induction of general anesthesia. Anesthesia was induced with propofol and remifentanil. Rocuronium was given in divided doses to obtain > 95% neuromuscular block to intubate the trachea. The ED50 and ED95 of rocuronium for this patient were 0.18 mg x kg(-1) and 0.39 mg x kg(-1), respectively. The values were similar to the ED50 and ED95 of rocuronium for normal patients. General anesthesia was maintained with propofol and remifentanil. Additional doses of rocuronium were given intermittently. Sugammadex, 2 mg x kg(-1), was given at the end of the surgery. The train-of-four ratio reached 93% 105 sec later. His postoperative course was uneventful. PMID:23984578

  11. Neuromuscular block after intra-arterially injected acetylcholine. 1. Introduction, methods, and technique.

    PubMed

    Tonali, P; Gambi, D

    1973-04-01

    The neuromuscular depolarizing block induced by intra-arterially injected ACh was studied to determine the variability in the same subject and in different subjects without disorders at the motor end-plate. Amplitude of action potentials of the opponens pollicis muscle evoked by intermittent repetitive supramaximal stimulation of the median nerve at the wrist were recorded for one hour from the beginning of ACh injection. The features of prompt and late depression stages after the injection were analysed statistically. Re-testing of the same subjects after a while shows that, in spite of all efforts to maintain the same experimental conditions, variations do occur in late depression. Time course and duration are particularly affected, while the degree of depression is altered but slightly. The presence of such variations limits this test to evaluation of the influence of other factors only within their already established statistical limits. PMID:4350703

  12. The neuromuscular blocking properties of a series of bis-quaternary tropeïnes

    PubMed Central

    Haining, C. G.; Johnston, R. G.; Smith, J. M.

    1960-01-01

    Linkage of two tropine esters through their nitrogen atoms by the chain -[CH2]m-O-CO-[CH2]n-CO-O-[CH2]m-, in which m was 2 or 3 and n varied from 0 to 6, gave compounds which produced neuromuscular block without depolarization. Reversibility be neostigmine was confirmed for a few compounds. Potency was found to depend upon the tropine ester employed and upon the values of n and m. Short duration and hypotensive properties were favoured by the higher values of n. The duration of action of the compound based on the phenylacetic acid ester of tropine, in which n=4 and m=2, varied considerably in different species. Epimerization, in which the relative positions of the methyl group and the linking chain on the quaternary tropane nitrogen atom were reversed, did not produce subtances having more favourable properties than those possessed by the unepimerized compounds. PMID:14398886

  13. Factors affecting magnitude and time course of neuromuscular block produced by suxamethonium.

    PubMed

    Vanlinthout, L E; van Egmond, J; de Boo, T; Lerou, J G; Wevers, R A; Booij, L H

    1992-07-01

    This study was designed to identify factors that significantly alter the magnitude and duration of suxamethonium-induced neuromuscular block in patients with an apparently normal genotype for pseudocholinesterase. One hundred and fifty-six adults (ages 18-65 yr) were allocated to 13 subgroups. Patients in each subgroup received suxamethonium 50-2000 micrograms kg-1. The mechanographic response of the adductor pollicis brevis muscle to ulnar nerve stimulation was recorded. The ED50 was found to be 167 micrograms kg-1, ED90 was 316 micrograms kg-1 and ED95 was 392 micrograms kg-1. The duration of action (delta t) was in agreement with earlier published results. The magnitude of block was dose-related and decreased with increasing onset time (ton) and pseudocholinesterase activity (PChA). Neither age nor gender affected the degree of suxamethonium-induced block. Delta t was dose-related, decreased with increasing PChA, and was shorter for women. Age and ton had no effect on delta t. PMID:1637599

  14. Neuromuscular dysfunction with the experimental arm acting as its own reference following eccentric and isometric exercise.

    PubMed

    Philippou, Anastassios; Bogdanis, Gregory C; Maridaki, Maria

    2010-01-01

    Eccentric exercise has been extensively used as a model to study muscle damage-induced neuromuscular impairment, adopting mainly a bilateral matching task between the reference (unexercised) arm and the indicator (exercised) arm. However, little attention has been given to the muscle proprioceptive function when the exercised arm acts as its own reference. This study investigated muscle proprioception and motor control, with the arm acting both as reference and indicator, following eccentric exercise and compared them with those observed after isometric exercise. Fourteen young male volunteers were equally divided into two groups and performed an eccentric or isometric exercise protocol with the elbow flexors of the non-dominant arm on an isokinetic dynamometer. Both exercise protocols induced significant changes in indicators of muscle damage, that is, muscle soreness, range of motion and maximal isometric force post-exercise (p < 0.05-0.001), and neuromuscular function was similarly affected following both protocols. Perception of force was impaired over the 4-day post-exercise period (p < 0.001), with the applied force being systematically overestimated. Perception of joint position was significantly disturbed (i.e., target angle was underestimated) only at one elbow angle on day 4 post-exercise (p < 0.05). The misjudgements and disturbed motor output observed when the exercised arm acted as its own reference concur with the view that they could be a result of a mismatch between the central motor command and an impaired motor control after muscle damage. PMID:20553224

  15. Exploring the link between pholcodine exposure and neuromuscular blocking agent anaphylaxis

    PubMed Central

    Brusch, Anna M; Clarke, Russell C; Platt, Peter R; Phillips, Elizabeth J

    2014-01-01

    Neuromuscular blocking agents (NMBAs) are the most commonly implicated drugs in IgE-mediated anaphylaxis during anaesthesia that can lead to perioperative morbidity and mortality. The rate of NMBA anaphylaxis shows marked geographical variation in patients who have had no known prior exposure to NMBAs, suggesting that there may be external or environmental factors that contribute to the underlying aetiology and pathophysiology of reactions. Substituted ammonium ions are shared among NMBAs and are therefore thought to be the main allergenic determinant of this class of drugs. Substituted ammonium ions are found in a wide variety of chemical structures, including prescription medications, over-the-counter medications and common household chemicals, such as the quaternary ammonium disinfectants. Epidemiological studies have shown parallels in the consumption of pholcodine, a nonprescription antitussive drug which contains a tertiary ammonium ion, and the incidence of NMBA anaphylaxis. This link has prompted the withdrawal of pholcodine in some countries, with an ensuing fall in the observed rate of NMBA anaphylaxis. While such observations are compelling in their suggestion of a relationship between pholcodine exposure and NMBA hypersensitivity, important questions remain regarding the mechanisms by which pholcodine is able to sensitize against NMBAs and whether there are other, as yet unidentified, agents that can elicit similar hypersensitivity reactions. This review aims to explore the evidence linking pholcodine exposure to NMBA hypersensitivity and discuss the implications for our understanding of the pathophysiology of these reactions. PMID:24251966

  16. Self-learning fuzzy control with temporal knowledge for atracurium-induced neuromuscular block during surgery.

    PubMed

    Mason, D G; Ross, J J; Edwards, N D; Linkens, D A; Reilly, C S

    1999-06-01

    Self-learning fuzzy logic control has the important property of accommodating uncertain, nonlinear, and time-varying process characteristics. This intelligent control scheme starts with no fuzzy control rules and learns how to control each process presented to it in real time without the need for detailed process modeling. In this study we utilize temporal knowledge of generated rules to improve control performance. A suitable medical application to investigate this control strategy is atracurium-induced neuromuscular block of patients in the operating theater where the patient response exhibits high nonlinearity and individual patient dose requirements may vary fivefold during an operating procedure. We developed a computer control system utilizing Relaxograph (Datex) measurements to assess the clinical performance of a self-learning fuzzy controller in this application. Using a T1 setpoint of 10% of baseline in 10 patients undergoing general surgery, we found a mean T1 error of 0.28% (SD = 0.39%) while accommodating a 0.25 to 0.38 mg/kg/h range in the mean atracurium infusion rate. This result compares favorably with more complex and computationally intensive model-based control strategies for atracurium infusion. PMID:10356301

  17. Effect of isoflurane and sevoflurane on the magnitude and time course of neuromuscular block produced by vecuronium, pancuronium and atracurium.

    PubMed

    Vanlinthout, L E; Booij, L H; van Egmond, J; Robertson, E N

    1996-03-01

    We have compared the ability of equipotent concentrations of isoflurane and sevoflurane to enhance the effect of non-depolarizing neuromuscular blocking drugs. Ninety ASA I and II patients of both sexes, aged 18-50 yr, were stratified into three blocker groups (Vec, Pan and Atr), to undergo neuromuscular block with vecuronium (n = 30), pancuronium (n = 30) or atracurium (n = 30), respectively. Within each group, patients were allocated randomly to one of three anaesthetic subgroups to undergo maintenance of anaesthesia with: (1) alfentanil-nitrous oxide-oxygen (n = 10); (2) alfentanil-nitrous oxide-oxygen-isoflurane (n = 10); or (3) alfentanil-nitrous oxide-oxygen-sevoflurane (n = 10) anaesthesia. During maintenance of anaesthesia, end-tidal concentrations of isoflurane, sevoflurane and nitrous oxide were 0.95, 1.70 and 70%, respectively. Both the evoked integrated electromyogram and mechanomyogram of the adductor pollicis brevis muscle were measured simultaneously. In the Vec and Pan groups, a total dose of 40 micrograms kg-1 of vecuronium or pancuronium, respectively, was given, and in the Atr group a total dose of atracurium 100 micrograms kg-1. Each blocker was given in four equal doses and administered cumulatively. We showed that 0.95% isoflurane and 1.70% sevoflurane (corresponding to 0.8 MAC of each inhalation anaesthetic, omitting the MAC contribution of nitrous oxide) augmented and prolonged the neuromuscular block produced by vecuronium, pancuronium and atracurium to a similar degree. PMID:8785139

  18. Neuromuscular block after intra-arterially injected acetylcholine. 2. Effects of ACTH treatments as possible detectors of desensitization level in the receptor site.

    PubMed

    Pinelli, P; Tonali, P; Gambi, D

    1973-04-01

    It has been suggested that the effect of ACTH in myasthenia gravis may be ascribed to an action involving neuromuscular transmission which favours repolarization processes, with a tendency towards hyperpolarization of the membranes of muscle fibres and motor nerve endings. A similar mechanism has been postulated for the action of ACTH in epilepsy (Klein, 1970). A direct or indirect action on nerve membrane would interfere with depolarization. There is evidence of raised concentration of intracellular potassium and increased outflow of sodium ions which would cause hyperpolarization of the membrane. This paper studies the effect of ACTH on the late block of neuromuscular transmission caused by acetylcholine (ACTH). PMID:4350704

  19. Elderly Patients Require Higher Doses of Sugammadex for Rapid Recovery from Deep Neuromuscular Block.

    PubMed

    Shin, Seokyung; Han, Dong Woo; Lee, Hye Sun; Song, Mi Kyung; Jun, Eun-Kyung; Kim, So Yeon

    2016-06-01

    This study compared the doses of sugammadex needed for rapid recovery from deep neuromuscular blockade (NMB) between young and elderly adults. Twenty-two young (20-40 yrs) and 22 elderly (≥70 yrs) adults were enrolled, and deep NMB of 1-2 post-tetanic counts was maintained with rocuronium intraoperatively. Predetermined doses of sugammadex were given at the end of surgery starting at 4.0 mg/kg for the first patient of each group. Doses were decreased or increased in following patients by 0.5 mg/kg, depending on the 'success' or 'failure' of rapid recovery in the preceding patient. 'Success' was defined as adequate recovery (train-of-four ratio 0.9) within 2 min. after sugammadex administration. The median (range) of ages was 29 (20-40) and 73 (70-84) yrs for the young and elderly adults, respectively. Doses of sugammadex facilitating adequate recovery from deep NMB within 2 min. in each patient population with 50% and 95% probability were defined as ED50 and ED95 , respectively. The ED50 estimated by the Dixon's method was significantly higher in the elderly compared to young adults [4.2 ± 0.4 mg/kg versus 3.3 ± 0.3 mg/kg, p < 0.001]. The ED50 (83% CI) estimated by isotonic regression was 4.5 (4.2-5.0) mg/kg in elderly adults and 3.3 (3.2-3.4) mg/kg in young adults. The ED95 (95% CI) estimated by isotonic regression was 5.4 (4.9-5.5) mg/kg and 4.4 (3.9-4.5) mg/kg in the elderly and young adults, respectively. In conclusion, dose adjustments of sugammadex should be considered when rapid recovery from deep NMB is needed in elderly adults. PMID:26505986

  20. A GABA-activated chloride-conductance not blocked by picrotoxin on spiny lobster neuromuscular preparations.

    PubMed Central

    Albert, J.; Lingle, C. J.; Marder, E.; O'Neil, M. B.

    1986-01-01

    Conductance increases to gamma-aminobutyric acid (GABA) were recorded in the gm6b and opener muscle of the spiny lobsters, Panulirus interruptus and P. argus. GABA-evoked responses were insensitive to picrotoxin at concentrations as high as 5 X 10(-5) M. Some blockade by picrotoxin was observed at higher concentrations. In normal physiological saline, the reversal potential of the Panulirus GABA-induced response was near the resting potential. The reversal potential was unaffected by reductions in sodium and calcium. Reduction of chloride by 50% resulted in a greater than 10 mV shift in the reversal potential of the GABA-induced response. Muscimol was able to mimic the action of GABA while baclofen was without effect. Bicuculline was a weak blocker. Avermectin B1a irreversibly increased the chloride permeability of the gm6b membrane. This conductance increase was blocked by picrotoxin over a range of concentrations similar to those required for blockade of the GABA-induced response. GABA-induced responses of the gm6b muscle of Homarus americanus were blocked almost completely by picrotoxin 10(-6) M. Sensitivity to picrotoxin is not invariably associated with GABA-activated chloride-mediated conductance increases. It is suggested that alteration in the binding-site for picrotoxin on the GABA-activated chloride-ion channel does not change other functional characteristics of the GABA-induced response. PMID:3708210

  1. Sugammadex compared with neostigmine/glycopyrrolate for routine reversal of neuromuscular block: a systematic review and economic evaluation†

    PubMed Central

    Paton, F.; Paulden, M.; Chambers, D.; Heirs, M.; Duffy, S.; Hunter, J. M.; Sculpher, M.; Woolacott, N.

    2010-01-01

    Summary The cost-effectiveness of sugammadex for the routine reversal of muscle relaxation produced by rocuronium or vecuronium in UK practice is uncertain. We performed a systematic review of randomized controlled trials of sugammadex compared with neostigmine/glycopyrrolate and an economic assessment of sugammadex for the reversal of moderate or profound neuromuscular block (NMB) produced by rocuronium or vecuronium. The economic assessment aimed to establish the reduction in recovery time and the ‘value of time saved’ which would be necessary for sugammadex to be potentially cost-effective compared with existing practice. Three trials indicated that sugammadex 2 mg kg−1 (4 mg kg−1) produces more rapid recovery from moderate (profound) NMB than neostigmine/glycopyrrolate. The economic assessment indicated that if the reductions in recovery time associated with sugammadex in the trials are replicated in routine practice, sugammadex would be cost-effective if those reductions are achieved in the operating theatre (assumed value of staff time, £4.44 per minute), but not if they are achieved in the recovery room (assumed value of staff time, £0.33 per minute). However, there is considerable uncertainty in these results. Sugammadex has the potential to be cost-effective compared with neostigmine/glycopyrrolate for the reversal of rocuronium-induced moderate or profound NMB, provided that the time savings observed in trials can be achieved and put to productive use in clinical practice. Further research is required to evaluate the effects of sugammadex on patient safety, predictability of recovery from NMB, patient outcomes, and efficient use of resources. PMID:20935005

  2. Effects of neuromuscular blocking agents and acetylcholinesterase inhibitors on the response of pectoral fin muscle of the sculpin (Enophrys bison) to indirect stimulation.

    PubMed

    Gant, D B; Weber, L J; Smith, J R

    1984-10-01

    The neuromuscular junction of the buffalo sculpin (Enophrys bison) was characterized in situ by examining the effects of various neuromuscular blocking agents and acetylcholinesterase inhibitors (ACHE-I) on pectoral muscle response to indirect stimulation. The injection of either d-tubocurarine (350 micrograms/kg) or alpha-bungarotoxin (alpha-Butx) (1 mg/kg) resulted in a flaccid paralysis. The depolarizing agents, succinylcholine (11 micrograms/kg) and decamethonium (42 micrograms/kg), produced a spontaneous contraction. The administration of the ACHE-I, diisopropyl fluorophosphate (DFP), and eserine resulted in responses which were contrary to those expected based on similar experiments using mammalian skeletal muscle. Twitch potentiation did not occur and the ability to maintain a tetanic response was not abolished even after the administration of clearly lethal concentrations of ACHE-I. PMID:6473351

  3. Anaesthetic tricaine acts preferentially on neural voltage-gated sodium channels and fails to block directly evoked muscle contraction.

    PubMed

    Attili, Seetharamaiah; Hughes, Simon M

    2014-01-01

    Movements in animals arise through concerted action of neurons and skeletal muscle. General anaesthetics prevent movement and cause loss of consciousness by blocking neural function. Anaesthetics of the amino amide-class are thought to act by blockade of voltage-gated sodium channels. In fish, the commonly used anaesthetic tricaine methanesulphonate, also known as 3-aminobenzoic acid ethyl ester, metacaine or MS-222, causes loss of consciousness. However, its role in blocking action potentials in distinct excitable cells is unclear, raising the possibility that tricaine could act as a neuromuscular blocking agent directly causing paralysis. Here we use evoked electrical stimulation to show that tricaine efficiently blocks neural action potentials, but does not prevent directly evoked muscle contraction. Nifedipine-sensitive L-type Cav channels affecting movement are also primarily neural, suggesting that muscle Nav channels are relatively insensitive to tricaine. These findings show that tricaine used at standard concentrations in zebrafish larvae does not paralyse muscle, thereby diminishing concern that a direct action on muscle could mask a lack of general anaesthesia. PMID:25090007

  4. Anaesthetic Tricaine Acts Preferentially on Neural Voltage-Gated Sodium Channels and Fails to Block Directly Evoked Muscle Contraction

    PubMed Central

    Attili, Seetharamaiah; Hughes, Simon M.

    2014-01-01

    Movements in animals arise through concerted action of neurons and skeletal muscle. General anaesthetics prevent movement and cause loss of consciousness by blocking neural function. Anaesthetics of the amino amide-class are thought to act by blockade of voltage-gated sodium channels. In fish, the commonly used anaesthetic tricaine methanesulphonate, also known as 3-aminobenzoic acid ethyl ester, metacaine or MS-222, causes loss of consciousness. However, its role in blocking action potentials in distinct excitable cells is unclear, raising the possibility that tricaine could act as a neuromuscular blocking agent directly causing paralysis. Here we use evoked electrical stimulation to show that tricaine efficiently blocks neural action potentials, but does not prevent directly evoked muscle contraction. Nifedipine-sensitive L-type Cav channels affecting movement are also primarily neural, suggesting that muscle Nav channels are relatively insensitive to tricaine. These findings show that tricaine used at standard concentrations in zebrafish larvae does not paralyse muscle, thereby diminishing concern that a direct action on muscle could mask a lack of general anaesthesia. PMID:25090007

  5. Effects of chronic treatment with various neuromuscular blocking agents on the number and distribution of acetylcholine receptors in the rat diaphragm.

    PubMed Central

    Chang, C C; Chuang, S T; Huang, M C

    1975-01-01

    1. Acetylcholine receptors in the end-plate and non-end-plate areas of the rat diaphragm, after treating the animal with hemicholinium-3, alpha- or beta-bungarotoxin in vivo, were studied by their specific binding of labelled alpha-bungarotoxin. 2. Subcutaneous injection of maximum tolerable doses of hemicholinium-3 (50 mug/kg) twice daily for 7 days increased the number of extrajunctional receptors along the whole length of muscle fibre, the approximate density of receptor on muscle membrane being increased from 6/mum2 in normal diaphragm to 38/mum2. Junctional receptors were also increased in number from 2-2 x 10(7) to 2-8 x 10(7) per end-plate. 3. Five days after denervation, there were approximately 153/mum2 extrajunctional receptors and the number of receptors on the end-plate was increased by 220%. 4. Intrathoracic injection of beta-bungarotoxin (50 mug/kg) also increased the density of extrajunctional receptors to approximately 104/mum2, and the number of end-plate receptors by 140% in 5 days. The neuromuscular block was extensive and prolonged. 5. [3H]Diacetyl alpha-bungarotoxin (150 mug/kg) injected into thoracic cavity caused complete neuromuscular blockade for 12 hr. At 24 hr, the synaptic transmission was restored in 80% of the junctions with less than 10% end-plate receptors freed, whereas the safety factor for transmission in normal diaphragm was 3-5. Extrajunctional receptors appeared to increase within 24 hr. This increase continued despite the restoration of neuromuscular transmission, and the receptor density at 5 days was approximately 5l/mum2. The number of junctional receptors, however, was not increased. Repeated injection of the toxin gave the same result. 6. It is concluded that the numbers of junctional and extrajunctional acetylcholine receptors are regulated in different ways, and the possible role of acetylcholine is discussed. PMID:170397

  6. [A Case of Rocuronium-induced Anaphylaxis in Which Surgery was Subsequently Performed under General Anesthesia without Neuromuscular Blocking Agents].

    PubMed

    Horiuchi, Tatsuo; Takazawa, Tomonori; Saito, Shigeru

    2016-03-01

    We report here a case of rocuronium-induced anaphylactic shock in a 41-year-old woman. She was scheduled for partial hepatectomy due to liver metastasis of a pheochromocytoma. Anesthesia was induced with propofol, remifentanil, and rocuronium. Bag-mask ventilation was difficult, and her blood pressure fell to around 40 mmHg just after induction. Subsequently, her trachea was intubated and adrenaline was injected. However, due to the subsequent persistence of severe hypotension and hypoxia, cardiopulmonary resuscitation was necessary. Suspecting the development of pulmonary embolism or anaphylaxis, we performed transesophageal echography; however, no evidence of right heart dilatation was observed, indicating a low possibility of pulmonary embolism. Although her general condition was stabilized, surgery was canceled. Blood tests showed high serum histamine and tryptase levels, suggesting an Ig-E mediated allergic reaction. A skin test performed five weeks after anesthesia suggested that she had suffered from rocuronium-induced anaphylaxis. A skin test also showed cross-reactivity between rocuronium and vecuronium. Therefore, we did not use any neuromuscular agent for the subsequent surgery, which was completed uneventfully. Determining the drug responsible for anaphylaxis helps to prevent recurrence of anaphylaxis. PMID:27097513

  7. Neuromuscular Scoliosis

    MedlinePlus

    ... degree of neuromuscular involvement. Diagnosis Incidence of Scoliosis Cerebral palsy (2 limbs involved) 25% Myelodysplasia (lower lumbar) 60% Spinal muscle atrophy 67% Friedreich ataxia 80% Cerebral palsy (4 limbs involved) 80% Duchenne muscular dystrophy 90% ...

  8. The role of the amino acid residue at α1:189 in the binding of neuromuscular blocking agents to mouse and human muscle nicotinic acetylcholine receptors

    PubMed Central

    Purohit, P G; Tate, R J; Pow, E; Hill, D; Connolly, J G

    2007-01-01

    Background and Purpose: Nicotinic acetylcholine receptors (AChRs) are valuable therapeutic targets. To exploit them fully requires rapid assays for the evaluation of potentially therapeutic ligands and improved understanding of the interaction of such ligands with their receptor binding sites. Experimental Approach: A variety of neuromuscular blocking agents (NMBAs) were tested for their ability to inhibit the binding of [125I]α-bungarotoxin to TE671 cells expressing human muscle AChRs. Association and dissociation rate constants for vecuronium inhibition of functional agonist responses were then estimated by electrophysiological studies on mouse muscle AChRs expressed in Xenopus oocytes containing either wild type or mutant α1 subunits. Key results: The TE671 inhibition binding assay allowed for the rapid detection of competitive nicotinic AChR ligands and the relative IC50 results obtained for NMBAs agreed well with clinical data. Electrophysiological studies revealed that acetylcholine EC50 values of muscle AChRs were not substantially altered by non-conservative mutagenesis of phenylalanine at α1:189 and proline at α1:194 to serine. However the α1:Phe189Ser mutation did result in a 3-4 fold increase in the rate of dissociation of vecuronium from mouse muscle AChRs. Conclusions and implications: The TE671 binding assay is a useful tool for the evaluation of potential therapeutic agents. The α1:Phe189Ser substitution, but not α1:Pro194Ser, significantly increases the rate of dissociation of vecuronium from mouse muscle AChRs. In contrast, these non-conservative mutations had little effect on EC50 values. This suggests that the AChR agonist binding site has a robust functional architecture, possibly as a result of evolutionary ‘reinforcement'. PMID:17293883

  9. Neuromuscular Blockade and Reversal Agents: A Primer for Postanesthesia Nurses.

    ERIC Educational Resources Information Center

    Pesci, Barbara R.

    1986-01-01

    Presents a comprehensive review of neuromuscular blocking agents, reversal agents used in anesthesia, and factors affecting reversal. It is aimed at nurses who provide care to patients recovering from anesthesia. It discusses the neuromuscular transmission system, depolarizing muscle relaxants, nondepolarizing blocking agents, and criteria for…

  10. Residual Neuromuscular Blockade.

    PubMed

    Plummer-Roberts, Anna L; Trost, Christina; Collins, Shawn; Hewer, Ian

    2016-02-01

    This article provides an update on residual neuromuscular blockade for nurse anesthetists. The neuromuscular junction, pharmacology for producing and reversing neuromuscular blockade, monitoring sites and methods, and patient implications relating to incomplete reversal of neuromuscular blockade are reviewed. Overall recommendations include using multiple settings when employing a peripheral nerve stimulator for monitoring return of neuromuscular function and administering pharmacologic reversal when the train-of-four ratio is below 0.9. PMID:26939390

  11. Dollars and Sense: Diverse Perspectives on Block Grants and the Personal Responsibility Act.

    ERIC Educational Resources Information Center

    Gardner, Sid; And Others

    In March 1995, the U.S. House of Representatives passed the Personal Responsibility Act (H.R. 4), part of the House Republican Contract with America. The bill would move primary responsibility for child and family programs to states and communities, reduce federal spending, and consolidate programs into block grants for child care, child…

  12. What Is the Evidence for Harm of Neuromuscular Blockade and Corticosteroid Use in the Intensive Care Unit?

    PubMed

    Annane, Djillali

    2016-02-01

    Neuromuscular blocking agents and corticosteroids are widely used in medicine and in particular in the intensive care unit (ICU). Neuromuscular blockade is commonly used to ease tracheal intubation, to optimize mechanical ventilation and oxygenation in acute respiratory disorders such as status asthmaticus and acute respiratory distress syndrome (ARDS), to prevent shivering during therapeutic hypothermia, and also in patients with elevated intracranial pressure. In the ICU, patients with sepsis, ARDS, community-acquired pneumonia, exacerbation of chronic obstructive pulmonary disease, severe asthma, or trauma may receive corticosteroids. It is not rare that ICU patients receive concomitantly neuromuscular blocking drugs and corticosteroids. Among the various serious adverse reactions to these drugs, secondary infection and ICU-acquired weakness may place a burden to the health-care system by resulting in substantial cost and long-term morbidity. Both superinfections and ICU-acquired paresis are more likely when high doses of fluorinated corticosteroids are combined with prolonged treatment with a long-acting non-depolarizing neuromuscular blocker. Modern ICU practices favor lower dose of corticosteroids and very short course of short-acting curare for the management of sepsis or ARDS. Recent trials provided no evidence for increased risk of secondary infections or critical illness neuromyopathy in patients with sepsis or ARDS with the use of corticosteroids or neuromuscular blockers. PMID:26820274

  13. Central enhancement of evoked electromyographic monitoring of neuromuscular function.

    PubMed

    Smith, D C

    1991-05-01

    Central neural influences on neuromuscular transmission may explain the frequent failure of evoked electromyographic (EEMG) responses to return to control values during offset of neuromuscular block. This study, performed in conscious subjects, did not demonstrate any change in EEMG response of either the first dorsal interosseous muscle during onset of ulnar nerve block or the flexor hallucis brevis during onset of subarachnoid block. It is concluded that central enhancement of EEMG response via a neural mechanism does not explain the observed failure of EEMG monitoring of neuromuscular block. PMID:1851627

  14. Neuromuscular blockade in the elderly patient

    PubMed Central

    Lee, Luis A; Athanassoglou, Vassilis; Pandit, Jaideep J

    2016-01-01

    Neuromuscular blockade is a desirable or even essential component of general anesthesia for major surgical operations. As the population continues to age, and more operations are conducted in the elderly, due consideration must be given to neuromuscular blockade in these patients to avoid possible complications. This review considers the pharmacokinetics and pharmacodynamics of neuromuscular blockade that may be altered in the elderly. Compartment distribution, metabolism, and excretion of drugs may vary due to age-related changes in physiology, altering the duration of action with a need for reduced dosage (eg, aminosteroids). Other drugs (atracurium, cisatracurium) have more reliable duration of action and should perhaps be considered for use in the elderly. The range of interpatient variability that neuromuscular blocking drugs may exhibit is then considered and drugs with a narrower range, such as cisatracurium, may produce more predictable, and inherently safer, outcomes. Ultimately, appropriate neuromuscular monitoring should be used to guide the administration of muscle relaxants so that the risk of residual neuromuscular blockade postoperatively can be minimized. The reliability of various monitoring is considered. This paper concludes with a review of the various reversal agents, namely, anticholinesterase drugs and sugammadex, and the alterations in dosing of these that should be considered for the elderly patient. PMID:27382330

  15. Sugammadex: A Review of Neuromuscular Blockade Reversal.

    PubMed

    Keating, Gillian M

    2016-07-01

    Sugammadex (Bridion(®)) is a modified γ-cyclodextrin that reverses the effect of the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. Intravenous sugammadex resulted in rapid, predictable recovery from moderate and deep neuromuscular blockade in patients undergoing surgery who received rocuronium or vecuronium. Recovery from moderate neuromuscular blockade was significantly faster with sugammadex 2 mg/kg than with neostigmine, and recovery from deep neuromuscular blockade was significantly faster with sugammadex 4 mg/kg than with neostigmine or spontaneous recovery. In addition, recovery from neuromuscular blockade was significantly faster when sugammadex 16 mg/kg was administered 3 min after rocuronium than when patients spontaneously recovered from succinylcholine. Sugammadex also demonstrated efficacy in various special patient populations, including patients with pulmonary disease, cardiac disease, hepatic dysfunction or myasthenia gravis and morbidly obese patients. Intravenous sugammadex was generally well tolerated. In conclusion, sugammadex is an important option for the rapid reversal of rocuronium- or vecuronium-induced neuromuscular blockade. PMID:27324403

  16. TEACHING NEUROMUSCULAR RELAXATION.

    ERIC Educational Resources Information Center

    NORRIS, JEANNE E.; STEINHAUS, ARTHUR H.

    THIS STUDY ATTEMPTED TO FIND OUT WHETHER (1) THE METHODS FOR ATTAINING NEUROMUSCULAR RELAXATION THAT HAVE PROVED FRUITFUL IN THE ONE-TO-ONE RELATIONSHIP OF THE CLINIC CAN BE SUCCESSFULLY ADAPTED TO THE TEACHER-CLASS RELATIONSHIP OF THE CLASSROOM AND GYMNASIUM, AND (2) NEUROMUSCULAR RELAXATION CAN BE TAUGHT SUCCESSFULLY BY AN APPROPRIATELY TRAINED…

  17. Neuromuscular complications in cancer.

    PubMed

    Grisold, W; Grisold, A; Löscher, W N

    2016-08-15

    Cancer is becoming a treatable and even often curable disease. The neuromuscular system can be affected by direct tumor invasion or metastasis, neuroendocrine, metabolic, dysimmune/inflammatory, infections and toxic as well as paraneoplastic conditions. Due to the nature of cancer treatment, which frequently is based on a DNA damaging mechanism, treatment related toxic side effects are frequent and the correct identification of the causative mechanism is necessary to initiate the proper treatment. The peripheral nervous system is conventionally divided into nerve roots, the proximal nerves and plexus, the peripheral nerves (mono- and polyneuropathies), the site of neuromuscular transmission and muscle. This review is based on the anatomic distribution of the peripheral nervous system, divided into cranial nerves (CN), motor neuron (MND), nerve roots, plexus, peripheral nerve, the neuromuscular junction and muscle. The various etiologies of neuromuscular complications - neoplastic, surgical and mechanic, toxic, metabolic, endocrine, and paraneoplastic/immune - are discussed separately for each part of the peripheral nervous system. PMID:27423586

  18. Femoral Nerve Block Versus Long-Acting Wound Infiltration in Total Knee Arthroplasty.

    PubMed

    Emerson, Roger H; Barrington, John W; Olugbode, Oluseun; Lovald, Scott; Watson, Heather; Ong, Kevin

    2016-05-01

    Multimodal wound infiltration analgesic techniques have attracted growing interest for applications in total knee arthroplasty (TKA). A benefit of using wound infiltration instead of femoral nerve block (FNB) in a multimodal pain control regimen is the limitation of muscle strength impairment to the surgical area, which will focus the pain control effort and may provide the opportunity for easier rehabilitation and earlier discharge from the hospital. The current study directly compares patients undergoing TKA who are given a continuous FNB with those who were administered an injection of liposomal bupivacaine infiltration. The study cohort included 36 patients with osteoarthritis who were treated with a continuous FNB (OnQ pump; I-Flow, Lake Forest, California), and 36 patients who were administered an injection for liposome bupivacaine infiltration (EXPAREL; Pacira Pharmaceuticals, Inc, Parsippany, New Jersey) for postoperative pain analgesia. The average number of narcotic doses and the total number of narcotics consumed was greater in the FNB group (P<.001). Average visual analog scale pain scores trended higher for patients in the FNB group (2.29 vs 1.93) overall and for each day postoperatively up to day 5, although the overall difference was not significant in this study sample (P=.115). The results of the current study support the conclusion that long-acting liposome bupivacaine infiltration gives comparable postoperative analgesia compared with a continuous FNB, but with significantly less narcotic medication. [Orthopedics. 2016; 39(3):e449-e455.]. PMID:27018607

  19. The effect of routine reversal of neuromuscular blockade on adequacy of recurrent laryngeal nerve stimulation during thyroid surgery.

    PubMed

    Marshall, S D; Boden, E; Serpell, J

    2015-07-01

    Testing of the integrity of the recurrent laryngeal nerve during thyroid surgery has become routine practice for many surgeons to aid dissection and minimise the chance of inadvertent nerve injury. We hypothesised that routine reversal of an intermediate-acting, non-depolarising neuromuscular blocking agent would improve conditions for stimulation of the recurrent laryngeal nerve. We conducted a single-centre, randomised, double-blind placebo-controlled trial of patients undergoing thyroid surgery by the same surgeon. After randomisation, the participants received either neostigmine 2.5 mg with glycopyrrolate 0.4 mg or placebo, at 30 minutes after induction of anaesthesia and administration of 0.4 mg/kg of atracurium. The primary outcome was the subjective assessment by the surgeon as to whether the neuromuscular function was adequate for stimulation of the recurrent laryngeal nerve using a neuromuscular integrity monitor (NIM). Time to NIM stimulation was 44.6 minutes in the placebo group and 41.4 minutes in the intervention group (P=0.268). Of the 21 patients who received the neuromuscular blockade reversal, 20 (95.2%) had adequate surgical conditions for NIM stimulation, compared to 9 out of 18 patients (50%) in the placebo group (P=0.002). Three of the ten patients (30%) with inadequate reversal showed no evidence of residual blockade assessed peripherally. The routine reversal of neuromuscular blockade at 30 minutes post induction appears to result in adequate surgical conditions for safe stimulation of the recurrent laryngeal nerve. Return of neuromuscular function at a peripheral site does not guarantee adequate laryngeal muscle function for use of the NIM. PMID:26099761

  20. ING1 and 5-Azacytidine Act Synergistically to Block Breast Cancer Cell Growth

    PubMed Central

    Thakur, Satbir; Feng, Xiaolan; Qiao Shi, Zhong; Ganapathy, Amudha; Kumar Mishra, Manoj; Atadja, Peter; Morris, Don; Riabowol, Karl

    2012-01-01

    Background Inhibitor of Growth (ING) proteins are epigenetic “readers” that recognize trimethylated lysine 4 of histone H3 (H3K4Me3) and target histone acetyl transferase (HAT) and histone deacetylase (HDAC) complexes to chromatin. Methods and Principal Findings Here we asked whether dysregulating two epigenetic pathways with chemical inhibitors showed synergistic effects on breast cancer cell line killing. We also tested whether ING1 could synergize better with chemotherapeutics that target the same epigenetic mechanism such as the HDAC inhibitor LBH589 (Panobinostat) or a different epigenetic mechanism such as 5-azacytidine (5azaC), which inhibits DNA methyl transferases. Simultaneous treatment of breast cancer cell lines with LBH589 and 5azaC did not show significant synergy in killing cells. However, combination treatment of ING1 with either LBH589 or 5azaC did show synergy. The combination of ING1b with 5azaC, which targets two distinct epigenetic mechanisms, was more effective at lower doses and enhanced apoptosis as determined by Annexin V staining and cleavage of caspase 3 and poly-ADP-ribose polymerase (PARP). ING1b plus 5azaC also acted synergistically to increase γH2AX staining indicating significant levels of DNA damage were induced. Adenoviral delivery of ING1b with 5azaC also inhibited cancer cell growth in a murine xenograft model and led to tumor regression when viral concentration was optimized in vivo. Conclusions These data show that targeting distinct epigenetic pathways can be more effective in blocking cancer cell line growth than targeting the same pathway with multiple agents, and that using viral delivery of epigenetic regulators can be more effective in synergizing with a chemical agent than using two chemotherapeutic agents. This study also indicates that the ING1 epigenetic regulator may have additional activities in the cell when expressed at high levels. PMID:22916295

  1. Neuromuscular disease in a dog.

    PubMed

    Bors, M; Valentine, B A; de Lahunta, A

    1988-10-01

    Diffuse neuromuscular disease occurs sporadically in dogs. The most commonly reported diffuse neuromuscular diseases are polyradiculoneuritis (coonhound paralysis), tick paralysis, botulism, and myasthenia gravis (1,2,12). This clinical report describes an atypical presentation of a diffuse neuromuscular disease in a dog. PMID:3168469

  2. Electrodiagnosis in neuromuscular disease.

    PubMed

    Lipa, Bethany M; Han, Jay J

    2012-08-01

    Electromyography (EMG) is an important diagnostic tool for the assessment of individuals with various neuromuscular diseases. It should be an extension of a thorough history and physical examination. Some prototypical characteristics and findings of EMG and nerve conduction studies are discussed; however, a more thorough discussion can be found in the textbooks and resources sited in the article. With an increase in molecular genetic diagnostics, EMG continues to play an important role in the diagnosis and management of patients with neuromuscular diseases and also provides a cost-effective diagnostic workup before ordering a battery of costly genetic tests. PMID:22938876

  3. Genetics and Neuromuscular Diseases

    MedlinePlus

    ... Neuromuscular Diseases • ©2011 MDA cell nucleus cell chromosomes DNA Genes are made of DNA, which is stored on chromo- somes in each ... particular protein. The effects of a mutation in DNA in a person depend on many fac- tors, ...

  4. [Fatigue in neuromuscular disease].

    PubMed

    Van Engelen, B G M; Kalkman, J S; Schillings, M L; Van Der Werf, S P; Bleijenberg, G; Zwarts, M J

    2004-07-01

    Chronic fatigue is a symptom of diseases such as cancer, multiple sclerosis, Parkinson's and cerebrovascular disease. Fatigue can also be present in people with no demonstrable somatic disease. If certain criteria are met, chronic-fatigue syndrome may be diagnosed in these cases. Fatigue is a multi-dimensional concept with physiological and psychological dimensions. The 'Short Fatigue Questionnaire' consisting of 4 questions is a tool to measure fatigue with a high degree of reliability and validity. Within the group of neuromuscular disorders, fatigue has been reported by patients with post-polio syndrome, myasthenia gravis, and Guillain-Barré syndrome. The percentage of neuromuscular patients suffering from severe fatigue (64%) is comparable with that of patients with multiple sclerosis, a disease in which fatigue is an acknowledged symptom. Now that reliable psychological and clinical neurophysiological techniques are available, a multidisciplinary approach to fatigue in patients with well-defined neuromuscular disorders may contribute towards the elucidation of the pathophysiological mechanisms of chronic fatigue, with the ultimate goal being to develop methods of treatment for fatigue in neuromuscular patients. PMID:15283024

  5. 76 FR 36143 - Central Utah Project Completion Act: Availability of Draft Environmental Assessment; Block Notice...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-21

    ..., Heber Sub-Area Irrigation to M&I Water Conversion, Wasatch County, UT AGENCY: Department of the Interior... Development Block Notice No. 1A and currently dedicated to the Heber Sub-Area from irrigation to municipal and industrial (M&I) use. The conversion would include up to 12,100 acre-feet of irrigation water in...

  6. Neuromuscular junctional disorders.

    PubMed

    Girija, A S; Ashraf, V V

    2008-07-01

    Neuromuscular junctional disorders (NMJ) in children are distinct entity. They may be acquired or hereditary. They pose problem in diagnosis because of the higher occurrence of sero negative Myasthenia Gravis (MG) cases in children. The identity of MusK antibody positivity in a good percentage of sero negative cases further adds to problems in diagnosis. The Congenital Myasthenic Syndrome (CMS) which are rare disorders of hereditary neuromuscular transmission (NMT) has to be differentiated because immunotherapy has no benefit in this group. Molecular genetic studies of these diseases helps to identify specific type of CMS which is important as other drugs like Fluoxetine, Quinidine are found to be effective in some. In infancy, all can manifest as floppy infant syndrome. The important key to diagnosis is by detailed electrophysiological studies including repetitive nerve stimulation at slow and high rates and its response to anticholinesterases and estimation of Acetyl choline receptor antibodies. Other causes of neuromuscular transmission defects viz. snake venom poisoning and that due to drugs are discussed. PMID:18716738

  7. 48 CFR 52.250-3 - SAFETY Act Block Designation/Certification.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... pursuant to 6 U.S.C. 442(d), as further delineated in 6 CFR 25.9, that a QATT for which a SAFETY Act... determination by DHS pursuant to 6 U.S.C. 441(b) and 6 U.S.C. 443(a), as further delineated in 6 CFR 25.4, that... review are based on the factors identified in 6 CFR 25.4(b). (e) Neither SAFETY Act designation...

  8. 48 CFR 52.250-3 - SAFETY Act Block Designation/Certification.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... pursuant to 6 U.S.C. 442(d), as further delineated in 6 CFR 25.9, that a QATT for which a SAFETY Act... determination by DHS pursuant to 6 U.S.C. 441(b) and 6 U.S.C. 443(a), as further delineated in 6 CFR 25.4, that... review are based on the factors identified in 6 CFR 25.4(b). (e) Neither SAFETY Act designation...

  9. 48 CFR 52.250-3 - SAFETY Act Block Designation/Certification.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... pursuant to 6 U.S.C. 442(d), as further delineated in 6 CFR 25.9, that a QATT for which a SAFETY Act... determination by DHS pursuant to 6 U.S.C. 441(b) and 6 U.S.C. 443(a), as further delineated in 6 CFR 25.4, that... review are based on the factors identified in 6 CFR 25.4(b). (e) Neither SAFETY Act designation...

  10. 48 CFR 52.250-3 - SAFETY Act Block Designation/Certification.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... pursuant to 6 U.S.C. 442(d), as further delineated in 6 CFR 25.9, that a QATT for which a SAFETY Act... determination by DHS pursuant to 6 U.S.C. 441(b) and 6 U.S.C. 443(a), as further delineated in 6 CFR 25.4, that... review are based on the factors identified in 6 CFR 25.4(b). (e) Neither SAFETY Act designation...

  11. 48 CFR 52.250-3 - SAFETY Act Block Designation/Certification.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... pursuant to 6 U.S.C. 442(d), as further delineated in 6 CFR 25.9, that a QATT for which a SAFETY Act... determination by DHS pursuant to 6 U.S.C. 441(b) and 6 U.S.C. 443(a), as further delineated in 6 CFR 25.4, that... review are based on the factors identified in 6 CFR 25.4(b). (e) Neither SAFETY Act designation...

  12. Computational Models for Neuromuscular Function

    PubMed Central

    Valero-Cuevas, Francisco J.; Hoffmann, Heiko; Kurse, Manish U.; Kutch, Jason J.; Theodorou, Evangelos A.

    2011-01-01

    Computational models of the neuromuscular system hold the potential to allow us to reach a deeper understanding of neuromuscular function and clinical rehabilitation by complementing experimentation. By serving as a means to distill and explore specific hypotheses, computational models emerge from prior experimental data and motivate future experimental work. Here we review computational tools used to understand neuromuscular function including musculoskeletal modeling, machine learning, control theory, and statistical model analysis. We conclude that these tools, when used in combination, have the potential to further our understanding of neuromuscular function by serving as a rigorous means to test scientific hypotheses in ways that complement and leverage experimental data. PMID:21687779

  13. Neuromuscular junction disorders.

    PubMed

    Verschuuren, Jan; Strijbos, Ellen; Vincent, Angela

    2016-01-01

    Diseases of the neuromuscular junction comprise a wide range of disorders. Antibodies, genetic mutations, specific drugs or toxins interfere with the number or function of one of the essential proteins that control signaling between the presynaptic nerve ending and the postsynaptic muscle membrane. Acquired autoimmune disorders of the neuromuscular junction are the most common and are described here. In myasthenia gravis, antibodies to acetylcholine receptors or to proteins involved in receptor clustering, particularly muscle-specific kinase, cause direct loss of acetylcholine receptors or interfere with the agrin-induced acetylcholine receptor clustering necessary for efficient neurotransmission. In the Lambert-Eaton myasthenic syndrome (LEMS), loss of the presynaptic voltage-gated calcium channels results in reduced release of the acetylcholine transmitter. The conditions are generally recognizable clinically and the diagnosis confirmed by serologic testing and electromyography. Screening for thymomas in myasthenia or small cell cancer in LEMS is important. Fortunately, a wide range of symptomatic treatments, immunosuppressive drugs, or other immunomodulating therapies is available. Future research is directed to understanding the pathogenesis, discovering new antigens, and trying to develop disease-specific treatments. PMID:27112691

  14. [Effect of cimetidine on neuromuscular blockade by succinylcholine and pancuronium].

    PubMed

    Sato, Y; Tsuchida, H; Harada, Y; Namiki, A

    1990-02-01

    The effect of cimetidine on neuromuscular blockade by succinylcholine and pancuronium was investigated in 54 adult patients scheduled for elective surgery. The neuromuscular blocking properties were estimated with single twitch height (T1) which was obtained by measuring the acceleration of adduction of the thumb in response to the ulnar nerve stimulation under N2O-fentanyl anesthesia. In cimetidine group, cimetidine 200 mg was administered orally on the night before surgery and 90 mins before anesthesia. Succinylcholine 1 mg.kg-1 (n = 14) or 1.5 mg.kg-1 (n = 20) was injected intravenously, and the onset time (from injection to 0% T1), the duration of maximal block (0% T1), and the recovery time from injection to 50% and 75% of control twitch height were evaluated. ED25 and ED50 of pancuronium were calculated from the dose response curve obtained by incremental administration of the drug (n = 20) whose total cumulative dose was 0.1 mg.kg-1. The recovery index of pancuronium was determined by measuring the 25%-75% recovery time. There was no significant difference between cimetidine pretreated patients and non-pretreated patients regarding these parameters of neuromuscular blockade with both succinylcholine and pancuronium. In conclusion, cimetidine has no influence on neuromuscular blockade of succinylcholine and pancuronium under N2O-fentanyl anesthesia. PMID:2325250

  15. ACTIONS OF TRIETHYLCHOLINE ON NEUROMUSCULAR TRANSMISSION

    PubMed Central

    Bowman, W C; Rand, M J

    1997-01-01

    The effects of the triethyl analogue of choline (triethyl 2-hydroxyethyl ammonium) on muscular activity have been studied in conscious rabbits, chicks, dogs and a cat. The contractions of the tibialis anticus and soleus muscles of cats under chloralose anaesthesia, and of the tibialis anticus muscle of rabbits under urethane anaesthesia and the isolated diaphragm preparation of the rat were also used. In conscious animals, triethylcholine caused a slowly developing muscular weakness which was more severe after exercise and which resembled the symptoms of myasthenia gravis. In nerve-muscle preparations triethylcholine had a selective action in reducing the contractions of muscles elicited by a high rate of nerve stimulation while leaving unaffected the contractions caused by slower rates of stimulation. During the paralysis of the tibialis muscle of the cat produced by triethylcholine, action potentials recorded from the motor nerve were unaffected and the muscle responded normally to injected acetylcholine and to direct electrical stimulation. The failure of neuromuscular transmission produced by triethylcholine was reversed by injection of choline, but anticholinesterases were ineffective. Choline reduced the toxicity of triethylcholine in mice. It is concluded that triethylcholine produces transmission failure at the neuromuscular junction by interfering with the ability of the nerve endings to synthesize acetylcholine. The possibility that triethylcholine is itself acetylated by the nerve endings and released as an inactive neurohormone is discussed. It was shown that triethylcholine was devoid of depolarizing action and curare-like blocking action. It possesses a transient ganglion blocking action of the tetraethylammonium-type as shown in experiments in which it caused a fall in blood pressure and blocked the response of the nictitating membrane to pre- but not to post-ganglionic stimulation of the cervical sympathetic nerve. PMID:9142408

  16. Mitochondria in neuromuscular disorders.

    PubMed

    DiMauro, S; Bonilla, E; Davidson, M; Hirano, M; Schon, E A

    1998-08-10

    This review considers primary mitochondrial diseases affecting the respiratory chain. As diseases due to mitochondrial DNA defects defy traditional anatomical classifications, we have not limited our discussion to neuromuscular disorders, but have extended it to include mitochondrial encephalomyopathies. Primary mitochondrial diseases can be due to mutations in either the nuclear or the mitochondrial genome. Nuclear mutations can affect (i) genes encoding enzymatic or structural mitochondrial proteins; (ii) translocases; (iii) mitochondrial protein importation; and (iv) intergenomic signaling. We review briefly recent molecular data and outstanding questions regarding these mendelian disorders, with special emphasis on cytochrome c oxidase deficiency and coenzyme Q10 deficiency. Mitochondrial DNA mutations fall into three main categories: (i) sporadic rearrangements (deletions/duplications); (ii) maternally inherited rearrangements (duplications); and (iii) maternally inherited point mutations. We summarize the most common clinical presentations and discuss pathogenic mechanisms, which remain largely elusive. Uncertainties about pathogenesis extend to the process of cell death, although excitotoxicity in neurons and apoptosis in muscle seem to have important roles. PMID:9714805

  17. Neuromuscular disease classification system

    NASA Astrophysics Data System (ADS)

    Sáez, Aurora; Acha, Begoña; Montero-Sánchez, Adoración; Rivas, Eloy; Escudero, Luis M.; Serrano, Carmen

    2013-06-01

    Diagnosis of neuromuscular diseases is based on subjective visual assessment of biopsies from patients by the pathologist specialist. A system for objective analysis and classification of muscular dystrophies and neurogenic atrophies through muscle biopsy images of fluorescence microscopy is presented. The procedure starts with an accurate segmentation of the muscle fibers using mathematical morphology and a watershed transform. A feature extraction step is carried out in two parts: 24 features that pathologists take into account to diagnose the diseases and 58 structural features that the human eye cannot see, based on the assumption that the biopsy is considered as a graph, where the nodes are represented by each fiber, and two nodes are connected if two fibers are adjacent. A feature selection using sequential forward selection and sequential backward selection methods, a classification using a Fuzzy ARTMAP neural network, and a study of grading the severity are performed on these two sets of features. A database consisting of 91 images was used: 71 images for the training step and 20 as the test. A classification error of 0% was obtained. It is concluded that the addition of features undetectable by the human visual inspection improves the categorization of atrophic patterns.

  18. Maintaining Optimal Surgical Conditions With Low Insufflation Pressures is Possible With Deep Neuromuscular Blockade During Laparoscopic Colorectal Surgery

    PubMed Central

    Kim, Myoung Hwa; Lee, Ki Young; Lee, Kang-Young; Min, Byung-Soh; Yoo, Young Chul

    2016-01-01

    Abstract Carbon dioxide (CO2) absorption and increased intra-abdominal pressure can adversely affect perioperative physiology and postoperative recovery. Deep muscle relaxation is known to improve the surgical conditions during laparoscopic surgery. We aimed to compare the effects of deep and moderate neuromuscular block in laparoscopic colorectal surgery, including intra-abdominal pressure. In this prospective, double-blind, parallel-group trial, 72 adult patients undergoing laparoscopic colorectal surgery were randomized using an online randomization generator to achieve either moderate (1–2 train-of-four response, n = 36) or deep (1–2 post-tetanic count, n = 36) neuromuscular block by receiving a continuous infusion of rocuronium. Adjusted intra-abdominal pressure, which was titrated by a surgeon with maintaining the operative field during pneumoperitoneum, was recorded at 5-minute intervals. Perioperative hemodynamic parameters and postoperative outcomes were assessed. Six patients from the deep and 5 from the moderate neuromuscular block group were excluded, leaving 61 for analysis. The average adjusted IAP was lower in the deep compared to the moderate neuromuscular block group (9.3 vs 12 mm Hg, P < 0.001). The postoperative pain scores (P < 0.001) and incidence of postoperative shoulder tip pain were lower, whereas gas passing time (P = 0.002) and sips of water time (P = 0.005) were shorter in the deep neuromuscular block than in the moderate neuromuscular block group. Deep neuromuscular blocking showed several benefits compared to conventional moderate neuromuscular block, including a greater intra-abdominal pressure lowering effect, whereas surgical conditions are maintained, less severe postoperative pain and faster bowel function recovery. PMID:26945393

  19. Sevoflurane enhances neuromuscular blockade by increasing the sensitivity of skeletal muscle to neuromuscular blockers

    PubMed Central

    Ye, Ling; Zuo, Yunxia; Zhang, Peng; Yang, Pingliang

    2015-01-01

    The aim of this study was to investigate the effects of sevoflurane on skeletal muscle contractility. In the first part, twenty-two American Society of Anesthesiology (ASA I-II) female adult patients undergoing elective hysterectomy surgery inhaled sevoflurane 1.0, 1.5 and 2.0 minimum alveolar concentrations (MAC) in succession. Neuromuscular function was assessed at each dose. In the second part, forty-four ASA I-II female adult patients were randomized into four groups: group 1 (propofol + atracurium, sevoflurane 0 MAC), and groups 2 to 4 (atracurium + sevoflurane 1.0, 1.5 and 2.0 MAC, respectively). In group 1, patients were anesthetized by propofol. Then 0.01 mg/kg atracurium was injected into the tested arm intravenously after the arterial blood flow was blocked using a tourniquet. For the other 3 groups, patients inhaled 1.0 MAC, 1.5 MAC, or 2.0 MAC of sevoflurane. Then 0.01 mg/kg atracurium was injected. Neuromuscular function was recorded for the 4 groups. Neuromuscular function was assessed by acceleromyography measurement of evoked responses to train-of four (TOF) stimuli (2 Hz for 2 s applied every 12 s) at the adductor pollicis using a TOF-GuardTM neuromuscular transmission monitor. Amplitudes of first response (T1) in each TOF sequence and the ratios of fourth TOF response (T4) to the first were similar at 1.0 MAC, 1.5 MAC, and 2.0 MAC sevoflurane. Compared to baseline, there was no significant change in the TOF value after inhaling 1.0 MAC, 1.5 MAC, or 2.0 MAC sevoflurane. Compared to group 1, there was no significant difference in atracurium onset time (time to reach TOF ratio = 0.25) in group 2 ( 5.6 ± 1.8 min vs. 6.5 ± 1.7 min, P>0.05), or degree of adductor pollicis block (subject number with TOF ratio = 0, 5 vs. 2 subjects, p = 0.3). However, inhaling 1.5 or 2.0 MAC sevoflurane decreased atracurium onset time (4.6 ± 1.5 min and 4.0 ± 1.3 min vs. 6.5 ± 1.7 min, P<0.01 and P<0.001, respectively), and enhanced the block degree (9 and 10 vs. 2

  20. Dengue-associated neuromuscular complications.

    PubMed

    Garg, Ravindra Kumar; Malhotra, Hardeep Singh; Jain, Amita; Malhotra, Kiran Preet

    2015-01-01

    Dengue is associated with many neurological dysfunctions. Up to 4% of dengue patients may develop neuromuscular complications. Muscle involvement can manifest with myalgias, myositis, rhabdomyolysis and hypokalemic paralysis. Diffuse myalgia is the most characteristic neurological symptom of dengue fever. Dengue-associated myositis can be of varying severity ranging from self-limiting muscle involvement to severe dengue myositis. Dengue-associated hypokalemic paralysis often has a rapidly evolving course; benign nature; excellent response to potassium; and, often leads to diagnostic confusion with other dengue-associated neuromuscular disorders. Rhabdomyolysis is the most severe form of muscle involvement and may be life-threatening. Guillain-Barrι syndrome is another frequent neuromuscular dengue-associated complication. Dengue-associated Guillain-Barrι syndrome responds very well to intravenous immunoglobulins. Predominant spinal gray matter involvement has been reported in a patient presenting with areflexic paraparesis. Mononeuropathies often manifest with paralysis of the diaphragm due to phrenic nerve dysfunction. Brachial plexopathy, in the form of neuralgic amyotrophy, has been described much more frequently than lumbo-sacral plexopathy. Early recognition of these neuromuscular complications is needed for successful treatment and to prevent further disabilities. PMID:26238884

  1. Adiposity, physical activity and neuromuscular performance in children.

    PubMed

    Haapala, Eero A; Väistö, Juuso; Lintu, Niina; Tompuri, Tuomo; Brage, Soren; Westgate, Kate; Ekelund, Ulf; Lampinen, Eeva-Kaarina; Sääkslahti, Arja; Lindi, Virpi; Lakka, Timo A

    2016-09-01

    We investigated the associations of body fat percentage (BF%), objectively assessed moderate-to-vigorous physical activity (MVPA) and different types of physical activity assessed by a questionnaire with neuromuscular performance. The participants were 404 children aged 6-8 years. BF% was assessed using dual-energy x-ray absorptiometry and physical activity by combined heart rate and movement sensing and a questionnaire. The results of 50-m shuttle run, 15-m sprint run, hand grip strength, standing long jump, sit-up, modified flamingo balance, box-and-block and sit-and-reach tests were used as measures of neuromuscular performance. Children who had a combination of higher BF% and lower levels of physical activity had the poorest performance in 50-m shuttle run, 15-m sprint run and standing long jump tests. Higher BF% was associated with slower 50-m shuttle run and 15-m sprint times, shorter distance jumped in standing long jump test, fewer sit-ups, more errors in balance test and less cubes moved in box-and-block test. Higher levels of physical activity and particularly MVPA assessed objectively by combined accelerometer and heart rate monitor were related to shorter 50-m shuttle run and 15-m sprint times. In conclusion, higher BF% and lower levels of physical activity and particularly the combination of these two factors were associated with worse neuromuscular performance. PMID:26734777

  2. Sustained Neuromuscular Blockade after Vecuronium Use in a Premature Infant

    PubMed Central

    Sahni, Mitali; Richardson, C. Joan; Jain, Sunil K.

    2015-01-01

    Background Prolonged use of neuromuscular blocking agents (NMBAs) is very common in critically ill children both in pediatric and neonatal intensive care units. There are no guidelines available for use of NMBAs in children or neonates in the US, and the data for their safety in this age group is limited. Case Description Our case describes prolonged neuromuscular blockade following concurrent use of a NMBA along with aminoglycosides and steroids in the setting of renal failure in a premature infant. Conclusion Prolonged use of NMBAs in preterm infants should be avoided if possible or should be restricted to the shortest possible duration and the smallest possible physiologically effective dose. Concurrent use of NMBAs with aminoglycoside and steroids should be avoided, especially in the setting of renal failure. PMID:26495168

  3. DYNAMIC NEUROMUSCULAR STABILIZATION & SPORTS REHABILITATION

    PubMed Central

    Kobesova, Alena; Kolar, Pavel

    2013-01-01

    Dynamic neuromuscular (core) stability is necessary for optimal athletic performance and is not achieved purely by adequate strength of abdominals, spinal extensors, gluteals or any other musculature; rather, core stabilization is accomplished through precise coordination of these muscles and intra‐abdominal pressure regulation by the central nervous system. Understanding developmental kinesiology provides a framework to appreciate the regional interdependence and the inter‐linking of the skeleton, joints, musculature during movement and the importance of training both the dynamic and stabilizing function of muscles in the kinetic chain. The Dynamic Neuromuscular Stabilization (DNS) approach provides functional tools to assess and activate the intrinsic spinal stabilizers in order to optimize the movement system for both pre‐habilitation and rehabilitation of athletic injuries and performance. Level of Evidence: 5 PMID:23439921

  4. [Respiratory treatments in neuromuscular disease].

    PubMed

    Martínez Carrasco, C; Cols Roig, M; Salcedo Posadas, A; Sardon Prado, O; Asensio de la Cruz, O; Torrent Vernetta, A

    2014-10-01

    In a previous article, a review was presented of the respiratory pathophysiology of the patient with neuromuscular disease, as well as their clinical evaluation and the major complications causing pulmonary deterioration. This article presents the respiratory treatments required to preserve lung function in neuromuscular disease as long as possible, as well as in special situations (respiratory infections, spinal curvature surgery, etc.). Special emphasis is made on the use of non-invasive ventilation, which is changing the natural history of many of these diseases. The increase in survival and life expectancy of these children means that they can continue their clinical care in adult units. The transition from pediatric care must be an active, timely and progressive process. It may be slightly stressful for the patient before the adaptation to this new environment, with multidisciplinary care always being maintained. PMID:24890888

  5. Neuromuscular Ultrasound of Cranial Nerves

    PubMed Central

    Tawfik, Eman A.; Cartwright, Michael S.

    2015-01-01

    Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed. PMID:25851889

  6. Tests of gastric neuromuscular function.

    PubMed

    Parkman, Henry P; Jones, Michael P

    2009-05-01

    Tests of gastric neuromuscular function are used to evaluate patients with symptoms referable to the upper digestive tract. These symptoms can be associated with alterations in the rates of gastric emptying, impaired accommodation, heightened gastric sensation, or alterations in gastric myoelectrical function and contractility. Management of gastric neuromuscular disorders requires an understanding of pathophysiology and treatment options as well as the appropriate use and interpretation of diagnostic tests. These tests include measures of gastric emptying; contractility; electrical activity; regional gastric motility of the fundus, antrum, and pylorus; and tests of sensation and compliance. Tests are also being developed to improve our understanding of the afferent sensory pathways from the stomach to the central nervous system that mediate gastric sensation in health and gastric disorders. This article reviews tests of gastric function and provides a basic description of the tests, the methodologies behind them, descriptions of the physiology that they assess, and their clinical utility. PMID:19293005

  7. Effect of 50% enantiomeric excess bupivacaine mixture combined with pancuronium on neuromuscular transmission in rat phrenic nerve-diaphragm preparation; a pilot study

    PubMed Central

    de Assunção Braga, Angelica de Fátima; Carvalho, Vanessa Henriques; da Silva Braga, Franklin Sarmento; Potério, Gloria Maria Braga; Santos, Filipe Nadir Caparica; Junqueira, Fernando Eduardo Féres

    2015-01-01

    Background and Aims: Local anaesthetics are drugs that are widely used in clinical practice. However, the effects of these drugs on the neuromuscular junction and their influence on the blockade produced by non-depolarising neuromuscular blocking drugs are still under investigation. The aim of this study was to evaluate, in vitro, the influence of a 50% enantiomeric excess bupivacaine mixture on neuromuscular transmission and neuromuscular block produced by pancuronium. Methods: Rats were distributed into three groups (n = 5) according to the drug studied namely, 50% enantiomeric excess bupivacaine mixture (5 μg/mL); pancuronium (2 μg/mL); 50% enantiomeric excess bupivacaine mixture + pancuronium. The following parameters were evaluated: (1) Effects of a 50% enantiomeric excess bupivacaine mixture on membrane potential (MP) and miniature endplate potentials (MEPPs); (2) amplitude of diaphragmatic response before and 60 min after the addition of a 50% enantiomeric excess bupivacaine mixture; the degree of neuromuscular block with pancuronium and pancuronium combined with a 50% enantiomeric excess bupivacaine mixture. Results: A 50% enantiomeric excess bupivacaine mixture did not alter the amplitude of muscle response (MP) but decreased the frequency and amplitude of MEPP. The block produced by pancuronium was potentiated by a 50% enantiomeric excess bupivacaine mixture. Conclusion: A 50% enantiomeric excess bupivacaine mixture used alone did not affect neuromuscular transmission, but potentiated the neuromuscular block produced by pancuronium. No action was shown on the muscle fibre, and alterations on MEPPs demonstrated a presynaptic action. PMID:26755834

  8. The clinical examination for neuromuscular disease.

    PubMed

    Glass, Eric N; Kent, Marc

    2002-01-01

    Neuromuscular disease can present even the most astute clinician with a challenging diagnostic dilemma. This article focuses on the neuroanatomy and the historical, physical, and neurologic examination findings observed in many of the neuromuscular disorders affecting dogs and cats. In addition, some common laboratory tests and imaging modalities used in the diagnosis of neuromuscular disease, including routine radiography, computed tomography, and magnetic resonance imaging, are discussed. A brief discussion of sensory nerve disorders is also presented. PMID:11785724

  9. American Association of Neuromuscular & Electrodiagnostic Medicine

    MedlinePlus

    ... Phenotype Severity and Mortality Advertisement Featured Resource: Self-Assessment Examinations Check out AANEM's self-assessment examinations (SAEs) for electrodiagnostic medicine and neuromuscular medicine. ...

  10. Musculoskeletal complications of neuromuscular disease in children.

    PubMed

    Driscoll, Sherilyn W; Skinner, Joline

    2008-02-01

    A wide variety of neuromuscular diseases affect children, including central nervous system disorders such as cerebral palsy and spinal cord injury; motor neuron disorders such as spinal muscular atrophy; peripheral nerve disorders such as Charcot-Marie-Tooth disease; neuromuscular junction disorders such as congenital myasthenia gravis; and muscle fiber disorders such as Duchenne's muscular dystrophy. Although the origins and clinical syndromes vary significantly, outcomes related to musculoskeletal complications are often shared. The most frequently encountered musculoskeletal complications of neuromuscular disorders in children are scoliosis, bony rotational deformities, and hip dysplasia. Management is often challenging to those who work with children who have neuromuscular disorders. PMID:18194756

  11. [Acute respiratory failure in neuromuscular disease].

    PubMed

    Damak, H; Décosterd, D

    2015-09-30

    Neuromuscular diseases can affect all respiratory muscles, leading to acute respiratory failure, which is the most common cause of morbidity and mortality in those patients. Two situations must be distinguished. 1) Acute respiratory failure as part of a neuromuscular disorder of acute onset and possibly reversible (Guillain-Barre syndrome, myasthenic crisis...). 2) Acute respiratory failure occurring in a patient with an already advanced neuromuscular disease (amyotrophic lateral sclerosis, Duchenne muscular dystrophy...). This article describes the neuromuscular acute respiratory failure in these different aspects, discusses its initial management in the emergency department and identifies the parameters that have to be monitored. PMID:26619704

  12. Neuromuscular Control and Coordination during Cycling

    ERIC Educational Resources Information Center

    Li, Li

    2004-01-01

    The neuromuscular control aspect of cycling has been investigated through the effects of modifying posture and cadence. These studies show that changing posture has a more profound influence on neuromuscular coordination than does changing slope. Most of the changes with standing posture occur late in the downstroke: increased ankle and knee joint…

  13. Common complications of pediatric neuromuscular disorders.

    PubMed

    Skalsky, Andrew J; Dalal, Pritha B

    2015-02-01

    Children with pediatric neuromuscular disorders experience common complications, primarily due to immobility and weakness. Musculoskeletal complications include hip dysplasia with associated hip subluxation or dislocation, neuromuscular scoliosis, and osteoporosis and resulting fractures. Constipation, gastroesophageal reflux, and obesity and malnutrition are commonly experienced gastrointestinal complications. Disordered sleep also is frequently observed, which affects both patients and caregivers. PMID:25479776

  14. Mitochondrial dysfunction in neuromuscular disorders.

    PubMed

    Katsetos, Christos D; Koutzaki, Sirma; Melvin, Joseph J

    2013-09-01

    This review deciphers aspects of mitochondrial (mt) dysfunction among nosologically, pathologically, and genetically diverse diseases of the skeletal muscle, lower motor neuron, and peripheral nerve, which fall outside the traditional realm of mt cytopathies. Special emphasis is given to well-characterized mt abnormalities in collagen VI myopathies (Ullrich congenital muscular dystrophy and Bethlem myopathy), megaconial congenital muscular dystrophy, limb-girdle muscular dystrophy type 2 (calpainopathy), centronuclear myopathies, core myopathies, inflammatory myopathies, spinal muscular atrophy, Charcot-Marie-Tooth neuropathy type 2, and drug-induced peripheral neuropathies. Among inflammatory myopathies, mt abnormalities are more prominent in inclusion body myositis and a subset of polymyositis with mt pathology, both of which are refractory to corticosteroid treatment. Awareness is raised about instances of phenotypic mimicry between cases harboring primary mtDNA depletion, in the context of mtDNA depletion syndrome, and established neuromuscular disorders such as spinal muscular atrophy. A substantial body of experimental work, derived from animal models, attests to a major role of mitochondria (mt) in the early process of muscle degeneration. Common mechanisms of mt-related cell injury include dysregulation of the mt permeability transition pore opening and defective autophagy. The therapeutic use of mt permeability transition pore modifiers holds promise in various neuromuscular disorders, including muscular dystrophies. PMID:24331362

  15. Airway clearance in neuromuscular weakness.

    PubMed

    Gauld, Leanne Maree

    2009-05-01

    Impaired airway clearance leads to recurrent chest infections and respiratory deterioration in neuromuscular weakness. It is frequently the cause of death. Cough is the major mechanism of airway clearance. Cough has several components, and assessment tools are available to measure the different components of cough. These include measuring peak cough flow, respiratory muscle strength, and inspiratory capacity. Each is useful in assessing the ability to generate an effective cough, and can be used to guide when techniques of assisting airway clearance may be effective for the individual and which are most effective. Techniques to assist airway clearance include augmenting inspiration by air stacking, augmenting expiration by assisting the cough, and augmenting both inspiration and expiration with the mechanical insufflator-exsufflator or by direct suctioning via a tracheostomy. Physiotherapists are invaluable in assisting airway clearance, and in teaching patients and their families how to use these techniques. Use of the mechanical insufflator-exsufflator has gained popularity in recent times, but several simpler, more economical methods are available to assist airway clearance that can be used effectively alone or in combination. This review examines the literature available on the assessment and management of impaired airway clearance in neuromuscular weakness. PMID:19379290

  16. Coenzyme Q10 Deficiencies in Neuromuscular Diseases

    PubMed Central

    Salviati, Leonardo; Jackson, Sandra; Hirano, Michio; Navas, Plácido

    2011-01-01

    Coenzyme Q (CoQ) is an essential component of the respiratory chain but also participates in other mitochondrial functions such as regulation of the transition pore and uncoupling proteins. Furthermore, this compound is a specific substrate for enzymes of the fatty acids β–oxidation pathway and pyrimidine nucleotide biosynthesis. Furthermore, CoQ is an antioxidant that acts in all cellular membranes and lipoproteins. A complex of at least ten nuclear (COQ) genes encoded proteins synthesizes CoQ but its regulation is unknown. Since 1989, a growing number of patients with multisystemic mitochondrial disorders and neuromuscular disorders showing deficiencies of CoQ have been identified. CoQ deficiency caused by muta-tion(s) in any of the COQ genes is designated primary deficiency. Other patients have displayed other genetic defects independent on the CoQ biosynthesis pathway, and are considered to have secondary deficiencies. This review updates the clinical and molecular aspects of both types of CoQ deficiencies and proposes new approaches to understanding their molecular bases. PMID:20225022

  17. Neuromuscular complications of hematopoietic stem cell transplantation.

    PubMed

    Ruzhansky, Katherine M; Brannagan, Thomas H

    2015-10-01

    Neuromuscular diseases such as polymyositis, dermatomyositis, peripheral neuropathy, and disorders of neuromuscular transmission are reported to be complications of hematopoietic stem cell transplantation (HSCT). Although cases have been reported with allogeneic HSCT in the setting of chronic graft versus host disease, they are also known to occur without evidence thereof and even occur in the setting of autologous HSCT. The 2005 National Institutes of Health Consensus Criteria classify polymyositis and dermatomyositis as "distinctive" features, and neuropathy and MG as "other" features. These neuromuscular complications present very similarly to the idiopathic autoimmune disorders and respond to similar treatment modalities. PMID:26044357

  18. Cough determinants in patients with neuromuscular disease.

    PubMed

    Trebbia, Grégoire; Lacombe, Mathieu; Fermanian, Christophe; Falaize, Line; Lejaille, Michèle; Louis, Alain; Devaux, Christian; Raphaël, Jean Claude; Lofaso, Frédéric

    2005-04-15

    Neuromuscular disease leads to cough impairment. Cough augmentation can be achieved by mechanical insufflation (MI) or manually assisted coughing (MAC). Many studies have compared these two methods, but few have evaluated them in combination. In 155 neuromuscular patients, we assessed determinants of peak cough flow (PCF) using stepwise correlation. Maximal inspiratory capacity contributed 44% of the variance (p<0.001), expiratory reserve volume 13%, and maximal expiratory pressure 2%. Thus, augmenting inspiration seems crucial. However, parameters dependent on expiratory muscles independently influence PCF. We measured vital capacity and PCF in 10 neuromuscular patients during cough augmentation by MI, MAC, or both. MI or MAC significantly improved VC and PCF (p<0.01) as compared to the basal condition and VC and PCF were higher during MI plus MAC than during MAC or MI alone (p<0.01). In conclusion, combining MAC and MI is useful for improving cough in neuromuscular patients. PMID:15766917

  19. Novel drug development for neuromuscular blockade.

    PubMed

    Prabhakar, Amit; Kaye, Alan D; Wyche, Melville Q; Salinas, Orlando J; Mancuso, Kenneth; Urman, Richard D

    2016-01-01

    Pharmacological advances in anesthesia in recent decades have resulted in safer practice and better outcomes. These advances include improvement in anesthesia drugs with regard to efficacy and safety profiles. Although neuromuscular blockers were first introduced over a half century ago, few new neuromuscular blockers and reversal agents have come to market and even fewer have remained as common clinically employed medications. In recent years, newer agents have been studied and are presented in this review. With regard to nondepolarizer neuromuscular blocker agents, the enantiomers Gantacurium and CW002, which are olefinic isoquinolinium diester fumarates, have shown potential for clinical application. Advantages include ultra rapid reversal of neuromuscular blockade via cysteine adduction and minimal systemic hemodynamic effects with administration. PMID:27625489

  20. Novel drug development for neuromuscular blockade

    PubMed Central

    Prabhakar, Amit; Kaye, Alan D; Wyche, Melville Q; Salinas, Orlando J; Mancuso, Kenneth; Urman, Richard D

    2016-01-01

    Pharmacological advances in anesthesia in recent decades have resulted in safer practice and better outcomes. These advances include improvement in anesthesia drugs with regard to efficacy and safety profiles. Although neuromuscular blockers were first introduced over a half century ago, few new neuromuscular blockers and reversal agents have come to market and even fewer have remained as common clinically employed medications. In recent years, newer agents have been studied and are presented in this review. With regard to nondepolarizer neuromuscular blocker agents, the enantiomers Gantacurium and CW002, which are olefinic isoquinolinium diester fumarates, have shown potential for clinical application. Advantages include ultra rapid reversal of neuromuscular blockade via cysteine adduction and minimal systemic hemodynamic effects with administration. PMID:27625489

  1. Neuromuscular Adaptations to Reduced Use

    NASA Technical Reports Server (NTRS)

    Ploutz-Snyder, Lori

    2009-01-01

    This viewgraph presentation reviews the studies done to reduce neuromuscular strength loss during unilateral lower limb suspension (ULLS). Since there are animals that undergo fairly long periods of muscular disuse without any or minimal muscular atrophy, there is an answer to that might be applicable to human in situations that require no muscular use to diminish the effects of muscular atrophy. Three sets of ULLS studies were reviewed indicated that muscle strength decreased more than the muscle mass. The study reviewed exercise countermeasures to combat the atrophy, including: ischemia maintained during Compound muscle action potential (CMAP), ischemia and low load exercise, Japanese kaatsu, and the potential for rehabilitation or situations where heavy loading is undesirable. Two forms of countermeasures to unloading have been successful, (1) high-load resistance training has maintained muscle mass and strength, and low load resistance training with blood flow restriction (LL(sub BFR)). The LL(sub BFR) has been shown to increase muscle mass and strength. There has been significant interest in Tourniquet training. An increase in Growth Hormone(GH) has been noted for LL(sub BFR) exercise. An experimental study with 16 subjects 8 of whom performed ULLS, and 8 of whom performed ULLS and LL(sub BFR) exercise three times per week during the ULLS. Charts show the results of the two groups, showing that performing LL(sub BFR) exercise during 30 days of ULLS can maintain muscle size and strength and even improve muscular endurance.

  2. Splicing therapy for neuromuscular disease.

    PubMed

    Douglas, Andrew G L; Wood, Matthew J A

    2013-09-01

    Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) are two of the most common inherited neuromuscular diseases in humans. Both conditions are fatal and no clinically available treatments are able to significantly alter disease course in either case. However, by manipulation of pre-mRNA splicing using antisense oligonucleotides, defective transcripts from the DMD gene and from the SMN2 gene in SMA can be modified to once again produce protein and restore function. A large number of in vitro and in vivo studies have validated the applicability of this approach and an increasing number of preliminary clinical trials have either been completed or are under way. Several different oligonucleotide chemistries can be used for this purpose and various strategies are being developed to facilitate increased delivery efficiency and prolonged therapeutic effect. As these novel therapeutic compounds start to enter the clinical arena, attention must also be drawn to the question of how best to facilitate the clinical development of such personalised genetic therapies and how best to implement their provision. PMID:23631896

  3. Protein defects in neuromuscular diseases.

    PubMed

    Vainzof, M; Zatz, M

    2003-05-01

    Muscular dystrophies are a heterogeneous group of genetically determined progressive disorders of the muscle with a primary or predominant involvement of the pelvic or shoulder girdle musculature. The clinical course is highly variable, ranging from severe congenital forms with rapid progression to milder forms with later onset and a slower course. In recent years, several proteins from the sarcolemmal muscle membrane (dystrophin, sarcoglycans, dysferlin, caveolin-3), from the extracellular matrix (alpha2-laminin, collagen VI), from the sarcomere (telethonin, myotilin, titin, nebulin), from the muscle cytosol (calpain 3, TRIM32), from the nucleus (emerin, lamin A/C, survival motor neuron protein), and from the glycosylation pathway (fukutin, fukutin-related protein) have been identified. Mutations in their respective genes are responsible for different forms of neuromuscular diseases. Protein analysis using Western blotting or immunohistochemistry with specific antibodies is of the utmost importance for the differential diagnosis and elucidation of the physiopathology of each genetic disorder involved. Recent molecular studies have shown clinical inter- and intra-familial variability in several genetic disorders highlighting the importance of other factors in determining phenotypic expression and the role of possible modifying genes and protein interactions. Developmental studies can help elucidate the mechanism of normal muscle formation and thus muscle regeneration. In the last fifteen years, our research has focused on muscle protein expression, localization and possible interactions in patients affected by different forms of muscular dystrophies. The main objective of this review is to summarize the most recent findings in the field and our own contribution. PMID:12715073

  4. Laparoscopic surgery and muscle relaxants: is deep block helpful?

    PubMed

    Kopman, Aaron F; Naguib, Mohamed

    2015-01-01

    It has been hypothesized that providing deep neuromuscular block (a posttetanic count of 1 or more, but a train-of-four [TOF] count of zero) when compared with moderate block (TOF counts of 1-3) for laparoscopic surgery would allow for the use of lower inflation pressures while optimizing surgical space and enhancing patient safety. We conducted a literature search on 6 different medical databases using 3 search strategies in each database in an attempt to find data substantiating this proposition. In addition, we studied the reference lists of the articles retrieved in the search and of other relevant articles known to the authors. There is some evidence that maintaining low inflation pressures during intra-abdominal laparoscopic surgery may reduce postoperative pain. Unfortunately most of the studies that come to these conclusions give few if any details as to the anesthetic protocol or the management of neuromuscular block. Performing laparoscopic surgery under low versus standard pressure pneumoperitoneum is associated with no difference in outcome with respect to surgical morbidity, conversion to open cholecystectomy, hemodynamic effects, length of hospital stay, or patient satisfaction. There is a limit to what deep neuromuscular block can achieve. Attempts to perform laparoscopic cholecystectomy at an inflation pressure of 8 mm Hg are associated with a 40% failure rate even at posttetanic counts of 1 or less. Well-designed studies that ask the question "is deep block superior to moderate block vis-à-vis surgical operating conditions" are essentially nonexistent. Without exception, all the peer-reviewed studies we uncovered which state that they investigated this issue have such serious flaws in their protocols that the authors' conclusions are suspect. However, there is evidence that abdominal compliance was not increased by a significant amount when deep block was established when compared with moderate neuromuscular block. Maintenance of deep block for

  5. When should sedation or neuromuscular blockade be used during mechanical ventilation?

    PubMed

    Bennett, Suzanne; Hurford, William E

    2011-02-01

    Sedation has become an important part of critical care practice in minimizing patient discomfort and agitation during mechanical ventilation. Pain, anxiety, and delirium form a triad of factors that can lead to agitation. Achieving and maintaining an optimal level of comfort and safety in the intensive care unit plays an essential part in caring for critically ill patients. Sedatives, opioids, and neuromuscular blocking agents are commonly used in the intensive care unit. The goal of therapy should be directed toward a specific indication, not simply to provide restraint. Standard rating scales and unit-based guidelines facilitate the proper use of sedation and neuromuscular blocking agents. The goal of sedation is a calm, comfortable patient who can easily be aroused and who can tolerate mechanical ventilation and procedures required for their care. PMID:21333177

  6. Employment profiles in neuromuscular diseases.

    PubMed

    Fowler, W M; Abresch, R T; Koch, T R; Brewer, M L; Bowden, R K; Wanlass, R L

    1997-01-01

    Consumer and rehabilitation provider factors that might limit employment opportunities for 154 individuals with six slowly progressive neuromuscular diseases (NMD) were investigated. The NMDs were spinal muscular atrophy (SMA), hereditary motor sensory neuropathy (HMSN), Becker's muscular dystrophy (BMD), facioscapulohumeral muscular dystrophy (FSHD), myotonic muscular dystrophy (MMD), and limb-girdle syndrome (LGS). Forty percent were employed in the competitive labor market at the time of the study, 50% had been employed in the past, and 10% had never been employed. The major consumer barrier to employment was education. Other important factors were type of occupation, intellectual capacity, psychosocial adjustment, and the belief by most individuals that their physical disability was the only or major barrier to obtaining a job. Psychological characteristics were associated with level of unemployment. However, physical impairment and disability were not associated with level of unemployment. There also were differences among the types of NMDs. Compared with the SMA, HMSN, BMD, and FSHD groups, the MMD and LGS groups had significantly higher levels of unemployment, lower educational levels, and fewer employed professional, management, and technical workers. Nonphysical impairment factors such as a low percentage of college graduates, impaired intellectual function in some individuals, and poor psychological adjustment were correlated with higher unemployment levels in the MMD group. Unemployment in the LGS group was correlated with a failure to complete high school. Major provider barriers to employment were the low level of referrals to Department of Rehabilitation by physicians and the low percentage of acceptance into the State Department of Rehabilitation. The low rate of acceptance was primarily attributable to the low number of referrals compounded by a lack of counselor experience with individuals with NMD. Both consumer and provider barriers may

  7. Flightless Flies: Drosophila models of neuromuscular disease

    PubMed Central

    Lloyd, Thomas E.; Taylor, J. Paul

    2010-01-01

    The fruit fly, Drosophila melanogaster, has a long and rich history as an important model organism for biologists. In particular, study of the fruit fly has been essential to much of our fundamental understanding of the development and function of the nervous system. In recent years, studies using fruit flies have provided important insights into the pathogenesis of neurodegenerative and neuromuscular diseases. Fly models of spinal muscular atrophy, spinobulbar muscular atrophy, myotonic dystrophy, dystrophinopathies and other inherited neuromuscular diseases recapitulate many of the key pathologic features of the human disease. The ability to perform genetic screens holds promise for uncovering the molecular mechanisms of disease, and indeed, for identifying novel therapeutic targets. This review will summarize recent progress in developing fly models of neuromuscular diseases and will emphasize the contribution that Drosophila has made to our understanding of these diseases. PMID:20329357

  8. Deep neuromuscular blockade leads to a larger intraabdominal volume during laparoscopy.

    PubMed

    Lindekaer, Astrid Listov; Halvor Springborg, Henrik; Istre, Olav

    2013-01-01

    Shoulder pain is a commonly reported symptom following laparoscopic procedures such as myomectomy or hysterectomy, and recent studies have shown that lowering the insufflation pressure during surgery may reduce the risk of post-operative pain. In this pilot study, a method is presented for measuring the intra-abdominal space available to the surgeon during laproscopy, in order to examine whether the relaxation produced by deep neuromuscular blockade can increase the working surgical space sufficiently to permit a reduction in the CO2 insufflation pressure. Using the laproscopic grasper, the distance from the promontory to the skin is measured at two different insufflation pressures: 8 mm Hg and 12 mm Hg. After the initial measurements, a neuromuscular blocking agent (rocuronium) is administered to the patient and the intra-abdominal volume is measured again. Pilot data collected from 15 patients shows that the intra-abdominal space at 8 mm Hg with blockade is comparable to the intra-abdominal space measured at 12 mm Hg without blockade. The impact of neuromuscular blockade was not correlated with patient height, weight, BMI, and age. Thus, using neuromuscular blockade to maintain a steady volume while reducing insufflation pressure may produce improved patient outcomes. PMID:23851450

  9. 21 CFR 882.5860 - Implanted neuromuscular stimulator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Implanted neuromuscular stimulator. 882.5860... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5860 Implanted neuromuscular stimulator. (a) Identification. An implanted neuromuscular stimulator is a device that...

  10. 21 CFR 882.5860 - Implanted neuromuscular stimulator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Implanted neuromuscular stimulator. 882.5860... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5860 Implanted neuromuscular stimulator. (a) Identification. An implanted neuromuscular stimulator is a device that...

  11. 21 CFR 882.5860 - Implanted neuromuscular stimulator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Implanted neuromuscular stimulator. 882.5860... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5860 Implanted neuromuscular stimulator. (a) Identification. An implanted neuromuscular stimulator is a device that...

  12. [Anesthetic Management of a Patient with Facioscapulohumeral Muscular Dystrophy: Importance of Monitoring Neuromuscular Function at Multiple Sites].

    PubMed

    Matsui, Shuhei; Tanaka, Satoshi; Kiyosawa, Kenkichi; Tanaka, Toshiyuki; Kawamata, Mikito

    2015-12-01

    A 39-year-old female with facioscapulohumeral muscular dystrophy (FSHD) was scheduled for thoracoscopic resection of an anterior mediastinal tumor. She had slowly progressive weakness and atrophy in the fascial and shoulder girdle muscles. General anesthesia was induced and maintained with propofol, remifentanil, and fentanyl combined with thoracic paravertebral block. Rocuronium-induced neuromuscular blockade was evaluated with acceleromyography at the corrugator supercilii, masseter, and adductor pollicis muscles. There was no reaction at the atrophic corrugator supercilii muscle in response to train-of-four (TOF) stimulation even before rocuronium administration. In contrast twitch responses at the masseter and adductor pollicis muscles to TOF stimulation could be evoked and the duration of action of rocuronium was found to be similar to that of the normal population. The perioperative course was uneventful. Neuromuscular monitoring sites should be carefully selected in FSHD patients because of possible inability to monitor neuromuscular function at the atrophic muscles. PMID:26790332

  13. Dynamic Flexibility and Proprioceptive Neuromuscular Facilitation.

    ERIC Educational Resources Information Center

    Hardy, Lew; Jones, David

    1986-01-01

    Two experiments are described which investigated whether results obtained in studies of static flexibility tranfer to dynamic flexibility. In both experiments, subjects were assigned to a group receiving proprioceptive neuromuscular facilitation training, ballistic stretching technique training or a control group. Results are presented and…

  14. Neuromuscular adaptations to respiratory muscle inactivity

    PubMed Central

    Mantilla, Carlos B.; Sieck, Gary C.

    2009-01-01

    Cervical spinal cord injury results in significant functional impairment. It is important to understand the neuroplasticity in response to inactivity of respiratory muscles in order to prevent any associated effects that limit functional recovery. Recent studies have examined the mechanisms involved in inactivity-induced neuroplasticity of diaphragm motor units. Both spinal hemisection at C2 (C2HS) and tetrodotoxin (TTX)-induced phrenic nerve blockade result in diaphragm paralysis and inactivity of axon terminals. However, phrenic motoneurons are inactive with C2HS but remain active after TTX. Diaphragm muscle fibers ipsilateral to C2HS display minimal changes post-injury. Neuromuscular transmission is enhanced following C2HS but impaired following TTX. Synaptic vesicle pool size at diaphragm neuromuscular junctions increases after C2HS, but decreases after TTX. Thus, inactivity-induced neuromuscular plasticity reflects specific adaptations that depend on inactivity at the motoneuron rather than at axon terminals or muscle fibers. Theses results indicate that neuromuscular transmission and functional properties of DIAm fibers can be maintained after spinal cord injury, providing a substrate for functional recovery and/or specific therapeutic approaches such as phrenic pacing. PMID:19744580

  15. Subcutaneous immunoglobulin in treating inflammatory neuromuscular disorders

    PubMed Central

    Yoon, Min-Suk; Gold, Ralf

    2015-01-01

    Objective: Intravenous immunoglobulin administration has long been used in the treatment of autoimmune neuromuscular disorders. Immunoglobulins may be administered by intramuscular, intravenous or subcutaneous routes. Methods: This is a report on the long-term clinical follow up of six patients with inflammatory neuromuscular disorders, that is, three chronic inflammatory demyelinating polyneuropathy (CIDP), one multifocal motor neuropathy (MMN), one inclusion body myositis (IBM) and one myasthenia gravis (MG), treated with subcutaneous immunoglobulins for a mean of 3.25 years. Results: One MMN and two CIDP patients received a weekly dose of subcutaneous immunoglobulins equivalent to intravenous immunoglobulin. One CIDP patient received a 50% dose reduction, the IBM patient received a 30% reduction and the MG patient a 20% reduction. The lower dose chosen in the majority of patients was based not only on clinical effects, but also on studies of primary immunodeficiency syndromes. One patient with CIDP showed clinical fluctuation, which was successfully treated with an adaptation of the dose of subcutaneous immunoglobulins, while the remaining patients with neuromuscular disorders had a stable clinical course for 2 years. No serious side effects were observed. Conclusions: Our results suggest that subcutaneous immunoglobulins can be an attractive alternative therapy in autoimmune neuromuscular disorders. PMID:26136842

  16. Linkage of Stress with Neuromuscular Disorders.

    PubMed

    Ashraf, Ghulam M; Ali, Ashraf; Tabrez, Shams; Zaidi, Syed Kashif; Shakil, Shazi; Alam, Mohammad Z; Rehan, Mohammad; Aliev, Gjumrakch

    2016-01-01

    Aging is associated with a progressive loss of muscle strength and mass, and a decline in neurophysiologic functions, which are characteristic features of neuromuscular disorders (NMDs). Understanding aging induced neuromuscular junction (NMJ) dysfunction is very crucial to understand the mechanism underlying NMDs. Morphological and physiological changes result in remodelling of the motor unit and a decline in the number of motor neuron muscle fibres. These alterations lead to excitation-contraction uncoupling and a loss of communication between the neuromuscular system, causing a decline in skeletal muscle strength and muscle mass. Understanding the molecular basis of NMJ dysfunction is essential in search for new treatment options. Besides structural and molecular studies, search for animal models to establish connection between brain and muscle is needed. Among various factors it has been observed that stress is one of the leading causes of NMDs. In the present review, we aim to explore various factors linking stress and NMDs neuromuscular disorders which gets aggravated by aging, with a special emphasis on mitochondrial connection. This in turn will help us gain new insights in the treatment of NMDs by aiding in improved symptoms, increased mobility and prolonged life. PMID:26831261

  17. Neuromuscular contributions to age-related weakness

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related physiological change of neuromuscular function is not a linear process and is likely influenced by various biological and behavioral factors (e.g., genetics, nutrition, physical activity level, comorbidities, etc.). These factors contribute to heterogeneity among older adults, which chal...

  18. The Human Homolog of Drosophila Headcase Acts as a Tumor Suppressor through Its Blocking Effect on the Cell Cycle in Hepatocellular Carcinoma

    PubMed Central

    Wang, Jun; Gong, Li; Zhu, Shao-Jun; Zhu, Qiao; Yao, Li; Han, Xiu-Juan; Zhang, Jia-Rui; Li, Yan-Hong; Zhang, Wei

    2015-01-01

    The molecular pathogenesis of hepatocellular carcinoma (HCC) is heterogeneous and extremely complex. Thus, for individual molecular targeted therapy, novel molecular markers are needed. The abnormal expression of the human homolog of Drosophila headcase (HECA homo) has been found in pancreatic, colorectal, and oral squamous cell carcinoma. Studies of oral squamous cell carcinoma have also demonstrated that the HECA homo protein can be negatively controlled by the Wnt-pathway and transcription factor 4 (TCF4) and can slow cell division by interacting with cyclins and CDKs. However, the role of HECA in HCC has not been reported elsewhere. Here, immunohistochemical analysis revealed that the downregulation of HECA homo protein occurred in 71.0% (66/93) of HCC cases and was positively correlated with a poorly differentiated grade, high serum AFP level, liver cirrhosis and large tumor size. The expression of HECA homo was detected in five live cell lines. In vitro, the overexpression of HECA homo in HepG2, Huh-7 and MHCC-97H cells could inhibit cell proliferation and colony formation and induce G1 phase arrest. In contrast, the downregulation of HECA homo could promote cell proliferation, colony formation and the cell cycle process. However, neither the overexpression nor downregulation of HECA homo in the three cell lines could affect cell migration or invasion. Collectively, HECA homo is regularly expressed in normal live cells, and the HECA homo protein level is heterogeneously altered in HCC, but the downregulation of HECA homo is more common and positively correlated with several malignant phenotypes. The HECA homo protein can slow cell proliferation to some extent primarily through its blocking effect on the cell cycle. Hence, the HECA homo protein may act as a tumor suppressor in HCC and might be a potential molecular marker for diagnostic classification and targeted therapy in HCC. PMID:26356417

  19. Short term modulation of trunk neuromuscular responses following spinal manipulation: a control group study

    PubMed Central

    2013-01-01

    Background Low back pain (LBP) is one of the most frequent musculoskeletal conditions in industrialized countries and its economic impact is important. Spinal manipulation therapy (SMT) is believed to be a valid approach in the treatment of both acute and chronic LBP. It has also been shown that SMT can modulate the electromyographic (EMG) activity of the paraspinal muscle. The purpose of this study was to investigate, in a group of patients with low back pain, the persistence of changes observed in trunk neuromuscular responses after a spinal manipulation (SMT). Methods Sixty adult participants with LBP performed a block of 5 flexion-extension movements. Participants in the experimental group (n=30) received lumbar SMT whereas participants in the control group (n=30) were positioned similarly for the treatment but did not receive SMT. Blocks of flexion-extension movements were repeated immediately after the manipulation as well as 5 and 30 minutes after SMT (or control position). EMG activity of paraspinal muscles was recorded at L2 and L5 level and kinematic data were collected to evaluate the lumbo-pelvic kinematics. Pain intensity was noted after each block. Normalized EMG, pain intensity and lumbo-pelvic kinematics were compared across experimental conditions. Results Participants from the control group showed a significant increase in EMG activity during the last block (30 min) of flexion-extension trials in both flexion and full-flexion phases at L2. Increase in VAS scores was also observed in the last 2 blocks (5 min and 30 min) in the control group. No significant group x time interaction was seen at L5. No significant difference was observed in the lumbo-pelvic kinematics. Conclusion Changes in trunk neuromuscular control following HVLA spinal manipulation may reduce sensitization or muscle fatigue effects related to repetitive movement. Future studies should investigate short term changes in neuromuscular components, tissue properties and clinical

  20. Heart Block

    MedlinePlus

    ... Block Explore Heart Block What Is... Electrical System & EKG Results Types Causes Who Is at Risk Signs & ... heart block. Doctors use a test called an EKG (electrocardiogram) to help diagnose heart block. This test ...

  1. [Genetic defects and disorders at the neuromuscular junction].

    PubMed

    Ohno, Kinji

    2011-07-01

    Genetic defects in molecules expressed at the neuromuscular junction (NMJ) cause congenital myasthenic syndromes (CMSs), which are characterized by muscle weakness, abnormal fatigability, amyotrophy, and minor facial anomalies. Muscle weakness mostly develops under 2 years but is also sometimes seen in adults. Mutations identified to date include (i) muscle nicotinic acetylcholine receptor (AChR) subunits, (ii) rapsyn that anchors and clusters AChRs at the neuromuscular junction, (iii) agrin that is released from the nerve terminal and induces AChR clustering by stimulating the downstream LRP4/MuSK/Dok-7/rapsyn/AChR pathway, (iv) muscle-specific kinase (MuSK) that transmits the AChR-clustering signal from agrin/LRP4 to rapsyn/AChR, (v) Dok-7 that transmits the AChR-clustering signal from agrin/LRP4/MuSK to rapsyn/AChR, (vi) skeletal muscle sodium channel type 1.4 (Nav1.4) that spreads the depolarization potential from the endplate throughout muscle fibers, (vii) collagen Q that anchors acetylcholinesterase to the synaptic basal lamina, and (viii) choline acetyltransferase that resynthesizes acetylcholine from recycled choline at the nerve terminal. In addition, mutations in the heparin sulfate proteoglycan perlecan, which binds to many molecules including collagen Q and dystroglycan, causes Schwartz-Jampel syndrome. Interestingly, mutations in LRP4 cause Cenani-Lenz syndactyly syndrome but not CMS. AChR, MuSK, and LRP4 are also targets of auto-antibodies in myasthenia gravis. In addition, molecules at the NMJ are targets of many other disease states AChRs are blocked by the snake toxin alpha-bungarotoxin and the plant poison curare. The presynaptic SNARE complex is attacked by botulinum toxin. Acetylcholinesterase is inhibited by the nerve gas sarin and by organophosphate pesticides. This review focuses on the molecular bases underlying defects of AChR, rapsyn, Nav1.4, collagen Q, and choline acetyltransferase. PMID:21747136

  2. Recovery from mivacurium-induced neuromuscular blockade is not affected by anticonvulsant therapy.

    PubMed

    Jellish, W S; Thalji, Z; Brundidge, P K; Tempelhoff, R

    1996-01-01

    Long-term chronic anticonvulsant therapy produces a resistance to the effects of all nondepolarizing neuromuscular blocking agents studied to date. Since the metabolism of mivacurium is unique among the nondepolarizing neuromuscular blocking agents, the effect of anticonvulsants on its recovery parameters was examined. Forty-five patients were separated into three groups based on the number of chronic anticonvulsant medications the subjects were taking: subjects in group 1, the control group, took no anticonvulsant medication; group 2 subjects took one medication; and group 3 subjects took two medications. Mivacurium, 0.15 mg/kg i.v., was administered after induction of general anesthesia with thiopental sodium, 4-6 mg/kg, and fentanyl 2-4 micrograms/kg i.v. Maintenance anesthesia consisted of N2O in O2. 0.2-0.3% end-tidal isoflurane, and a fentanyl infusion. The evoked compound electromyograph (ECEMG) of the adductor pollicis-brevis muscle was measured for time of onset, T-1 (time at which ECEMG signal reaches 5, 25, 50, and 75% of baseline), TR (TOF ratio), and recovery index. T-1 at 25% was 18.2 +/- 1.8, 20.7 +/- 1.9, and 21.5 +/- 1.4 min for groups 1, 2, and 3, respectively, with TR at 25% being 23.7 +/- 2.3, 26.9 +/- 2.4, and 27.3 +/- 2.3 min. No significant differences were noted in neuromuscular recovery between groups at any time point. These results fail to demonstrate the resistance to the nondepolarizing neuromuscular blockade of mivacurium that has been observed with other nondepolarizing agents. PMID:8719185

  3. Adaptive Inverse optimal neuromuscular electrical stimulation.

    PubMed

    Wang, Qiang; Sharma, Nitin; Johnson, Marcus; Gregory, Chris M; Dixon, Warren E

    2013-12-01

    Neuromuscular electrical stimulation (NMES) is a prescribed treatment for various neuromuscular disorders, where an electrical stimulus is provided to elicit a muscle contraction. Barriers to the development of NMES controllers exist because the muscle response to an electrical stimulation is nonlinear and the muscle model is uncertain. Efforts in this paper focus on the development of an adaptive inverse optimal NMES controller. The controller yields desired limb trajectory tracking while simultaneously minimizing a cost functional that is positive in the error states and stimulation input. The development of this framework allows tradeoffs to be made between tracking performance and control effort by putting different penalties on error states and control input, depending on the clinical goal or functional task. The controller is examined through a Lyapunov-based analysis. Experiments on able-bodied individuals are provided to demonstrate the performance of the developed controller. PMID:23757569

  4. Gastrointestinal neuromuscular pathology in chronic constipation

    PubMed Central

    Knowles, Charles H.; Farrugia, Gianrico

    2014-01-01

    Some patients with chronic constipation may undergo colectomy yielding tissue appropriate to diagnosis of underlying neuromuscular pathology. The analysis of such tissue has, over the past 40 years, fuelled research that has explored the presence of neuropathy, myopathy and more recently changes in interstitial cells of Cajal (ICC). In this chapter, the data from these studies have been critically reviewed in the context of the significant methodological and interpretative issues that beset the field of gastrointestinal neuromuscular pathology. On this basis, reductions in ICC appear to a consistent finding but one whose role as a primary cause of slow transit constipation requires further evaluation. Findings indicative of significant neuropathy or myopathy are variable and in many studies subject to considerable methodological bias. Methods with practical diagnostic utility in the individual patient have rarely been employed and require further validation in respect of normative data. PMID:21382578

  5. Gene and splicing therapies for neuromuscular diseases.

    PubMed

    Benchaouir, Rachid; Robin, Valerie; Goyenvalle, Aurelie

    2015-01-01

    Neuromuscular disorders (NMD) are heterogeneous group of genetic diseases characterized by muscle weakness and wasting. Duchenne Muscular dystrophy (DMD) and Spinal muscular atrophy (SMA) are two of the most common and severe forms in humans and although the molecular mechanisms of these diseases have been extensively investigated, there is currently no effective treatment. However, new gene-based therapies have recently emerged with particular noted advances in using conventional gene replacement strategies and RNA-based technology. Whilst proof of principle have been demonstrated in animal models, several clinical trials have recently been undertaken to investigate the feasibility of these strategies in patients. In particular, antisense mediated exon skipping has shown encouraging results and hold promise for the treatment of dystrophic muscle. In this review, we summarize the recent progress of therapeutic approaches to neuromuscular diseases, with an emphasis on gene therapy and splicing modulation for DMD and SMA, focusing on the advantages offered by these technologies but also their challenges. PMID:25961553

  6. Neuromuscular Electrical Stimulation for Skeletal Muscle Function

    PubMed Central

    Doucet, Barbara M.; Lam, Amy; Griffin, Lisa

    2012-01-01

    Lack of neural innervation due to neurological damage renders muscle unable to produce force. Use of electrical stimulation is a medium in which investigators have tried to find a way to restore movement and the ability to perform activities of daily living. Different methods of applying electrical current to modify neuromuscular activity are electrical stimulation (ES), neuromuscular electrical stimulation (NMES), transcutaneous electrical nerve stimulation (TENS), and functional electrical stimulation (FES). This review covers the aspects of electrical stimulation used for rehabilitation and functional purposes. Discussed are the various parameters of electrical stimulation, including frequency, pulse width/duration, duty cycle, intensity/amplitude, ramp time, pulse pattern, program duration, program frequency, and muscle group activated, and how they affect fatigue in the stimulated muscle. PMID:22737049

  7. Neuromuscular adaptation to actual and simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Edgerton, V. R.; Roy, R. R.

    1994-01-01

    The chronic "unloading" of the neuromuscular system during spaceflight has detrimental functional and morphological effects. Changes in the metabolic and mechanical properties of the musculature can be attributed largely to the loss of muscle protein and the alteration in the relative proportion of the proteins in skeletal muscle, particularly in the muscles that have an antigravity function under normal loading conditions. These adaptations could result in decrements in the performance of routine or specialized motor tasks, both of which may be critical for survival in an altered gravitational field, i.e., during spaceflight and during return to 1 G. For example, the loss in extensor muscle mass requires a higher percentage of recruitment of the motor pools for any specific motor task. Thus, a faster rate of fatigue will occur in the activated muscles. These consequences emphasize the importance of developing techniques for minimizing muscle loss during spaceflight, at least in preparation for the return to 1 G after spaceflight. New insights into the complexity and the interactive elements that contribute to the neuromuscular adaptations to space have been gained from studies of the role of exercise and/or growth factors as countermeasures of atrophy. The present chapter illustrates the inevitable interactive effects of neural and muscular systems in adapting to space. It also describes the considerable progress that has been made toward the goal of minimizing the functional impact of the stimuli that induce the neuromuscular adaptations to space.

  8. Dok-7 mutations underlie a neuromuscular junction synaptopathy.

    PubMed

    Beeson, David; Higuchi, Osamu; Palace, Jackie; Cossins, Judy; Spearman, Hayley; Maxwell, Susan; Newsom-Davis, John; Burke, Georgina; Fawcett, Peter; Motomura, Masakatsu; Müller, Juliane S; Lochmüller, Hanns; Slater, Clarke; Vincent, Angela; Yamanashi, Yuji

    2006-09-29

    Congenital myasthenic syndromes (CMSs) are a group of inherited disorders of neuromuscular transmission characterized by fatigable muscle weakness. One major subgroup of patients shows a characteristic "limb girdle" pattern of muscle weakness, in which the muscles have small, simplified neuromuscular junctions but normal acetylcholine receptor and acetylcholinesterase function. We showed that recessive inheritance of mutations in Dok-7, which result in a defective structure of the neuromuscular junction, is a cause of CMS with proximal muscle weakness. PMID:16917026

  9. Neuromuscular Disease in the Neurointensive Care Unit.

    PubMed

    Crespo, Veronica; James, Michael L Luke

    2016-09-01

    Neuromuscular diseases are syndromic disorders that affect nerve, muscle, and/or neuromuscular junction. Knowledge about the management of these diseases is required for anesthesiologists, because these may frequently be encountered in the intensive care unit, operating room, and other settings. The challenges and advances in management for some of the neuromuscular diseases most commonly encountered in the operating room and neurointensive care unit are reviewed. PMID:27521200

  10. LRP4 is critical for neuromuscular junction maintenance.

    PubMed

    Barik, Arnab; Lu, Yisheng; Sathyamurthy, Anupama; Bowman, Andrew; Shen, Chengyong; Li, Lei; Xiong, Wen-cheng; Mei, Lin

    2014-10-15

    The neuromuscular junction (NMJ) is a synapse between motor neurons and skeletal muscle fibers, and is critical for control of muscle contraction. Its formation requires neuronal agrin that acts by binding to LRP4 to stimulate MuSK. Mutations have been identified in agrin, MuSK, and LRP4 in patients with congenital myasthenic syndrome, and patients with myasthenia gravis develop antibodies against agrin, LRP4, and MuSK. However, it remains unclear whether the agrin signaling pathway is critical for NMJ maintenance because null mutation of any of the three genes is perinatal lethal. In this study, we generated imKO mice, a mutant strain whose LRP4 gene can be deleted in muscles by doxycycline (Dox) treatment. Ablation of the LRP4 gene in adult muscle enabled studies of its role in NMJ maintenance. We demonstrate that Dox treatment of P30 mice reduced muscle strength and compound muscle action potentials. AChR clusters became fragmented with diminished junctional folds and synaptic vesicles. The amplitude and frequency of miniature endplate potentials were reduced, indicating impaired neuromuscular transmission and providing cellular mechanisms of adult LRP4 deficiency. We showed that LRP4 ablation led to the loss of synaptic agrin and the 90 kDa fragments, which occurred ahead of other prejunctional and postjunctional components, suggesting that LRP4 may regulate the stability of synaptic agrin. These observations demonstrate that LRP4 is essential for maintaining the structural and functional integrity of the NMJ and that loss of muscle LRP4 in adulthood alone is sufficient to cause myasthenic symptoms. PMID:25319686

  11. LRP4 Is Critical for Neuromuscular Junction Maintenance

    PubMed Central

    Barik, Arnab; Lu, Yisheng; Sathyamurthy, Anupama; Bowman, Andrew; Shen, Chengyong; Li, Lei; Xiong, Wen-cheng

    2014-01-01

    The neuromuscular junction (NMJ) is a synapse between motor neurons and skeletal muscle fibers, and is critical for control of muscle contraction. Its formation requires neuronal agrin that acts by binding to LRP4 to stimulate MuSK. Mutations have been identified in agrin, MuSK, and LRP4 in patients with congenital myasthenic syndrome, and patients with myasthenia gravis develop antibodies against agrin, LRP4, and MuSK. However, it remains unclear whether the agrin signaling pathway is critical for NMJ maintenance because null mutation of any of the three genes is perinatal lethal. In this study, we generated imKO mice, a mutant strain whose LRP4 gene can be deleted in muscles by doxycycline (Dox) treatment. Ablation of the LRP4 gene in adult muscle enabled studies of its role in NMJ maintenance. We demonstrate that Dox treatment of P30 mice reduced muscle strength and compound muscle action potentials. AChR clusters became fragmented with diminished junctional folds and synaptic vesicles. The amplitude and frequency of miniature endplate potentials were reduced, indicating impaired neuromuscular transmission and providing cellular mechanisms of adult LRP4 deficiency. We showed that LRP4 ablation led to the loss of synaptic agrin and the 90 kDa fragments, which occurred ahead of other prejunctional and postjunctional components, suggesting that LRP4 may regulate the stability of synaptic agrin. These observations demonstrate that LRP4 is essential for maintaining the structural and functional integrity of the NMJ and that loss of muscle LRP4 in adulthood alone is sufficient to cause myasthenic symptoms. PMID:25319686

  12. Neuromuscular function in different stages of sarcopenia.

    PubMed

    Morat, Tobias; Gilmore, Kevin J; Rice, Charles L

    2016-08-01

    This study applied the screening tool developed by the European Working Group on Sarcopenia in Older People (EWGSOP) on seniors aged over 65years and concurrently tested various laboratory-based indices of neuromuscular function. Twenty-four healthy and independent living older adults (9 men, 15 women) with a mean age of 79.1±5.8years participated. Based on gait speed, handgrip strength and muscle mass all subjects were categorized into one of the three conceptual sarcopenia stages (pre-sarcopenia, sarcopenia, severe sarcopenia). Maximal strength of dorsiflexors in the left leg was measured and voluntary activation was assessed by the interpolated twitch technique. In addition, isometric evoked contractile properties were recorded. Skeletal muscle mass was assessed by ultrasound from nine sites. There were roughly equal number of subjects in each sarcopenic category, and age was not different among the 3 groups. There were no differences in handgrip strength and skeletal muscle mass index among the 3 groups. Gait speed was significantly slower (p<0.01) in the severe sarcopenic subjects compared to the pre-sarcopenic group. With no differences in voluntary activation among the groups, the maximal voluntary contractions (MVCs) for severe sarcopenic subjects were 29% lower (p=0.02) and with 19% slower (p=0.02) voluntary rates of torque development (RTD) compared to sarcopenic subjects. Furthermore, the severe group was 34% lower (p=0.04) with 36% slower (p=0.02) RTD compared to pre-sarcopenic subjects. Peak twitch tension was 54% lower (p<0.01) in the severe group compared with the pre-sarcopenic group. Maximal twitch RTD were 40% (p=0.03) slower for the severe group compared to the sarcopenia group, and 51% slower (p=0.03) compared with the pre-sarcopenia group, but when normalized to peak torques there were no statistical differences. The laboratory tests found neuromuscular differences among the 3 groups which generally supported the classification scheme and

  13. A Markov computer simulation model of the economics of neuromuscular blockade in patients with acute respiratory distress syndrome

    PubMed Central

    Macario, Alex; Chow, John L; Dexter, Franklin

    2006-01-01

    Background Management of acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) is clinically challenging and costly. Neuromuscular blocking agents may facilitate mechanical ventilation and improve oxygenation, but may result in prolonged recovery of neuromuscular function and acute quadriplegic myopathy syndrome (AQMS). The goal of this study was to address a hypothetical question via computer modeling: Would a reduction in intubation time of 6 hours and/or a reduction in the incidence of AQMS from 25% to 21%, provide enough benefit to justify a drug with an additional expenditure of $267 (the difference in acquisition cost between a generic and brand name neuromuscular blocker)? Methods The base case was a 55 year-old man in the ICU with ARDS who receives neuromuscular blockade for 3.5 days. A Markov model was designed with hypothetical patients in 1 of 6 mutually exclusive health states: ICU-intubated, ICU-extubated, hospital ward, long-term care, home, or death, over a period of 6 months. The net monetary benefit was computed. Results Our computer simulation modeling predicted the mean cost for ARDS patients receiving standard care for 6 months to be $62,238 (5% – 95% percentiles $42,259 – $83,766), with an overall 6-month mortality of 39%. Assuming a ceiling ratio of $35,000, even if a drug (that cost $267 more) hypothetically reduced AQMS from 25% to 21% and decreased intubation time by 6 hours, the net monetary benefit would only equal $137. Conclusion ARDS patients receiving a neuromuscular blocker have a high mortality, and unpredictable outcome, which results in large variability in costs per case. If a patient dies, there is no benefit to any drug that reduces ventilation time or AQMS incidence. A prospective, randomized pharmacoeconomic study of neuromuscular blockers in the ICU to asses AQMS or intubation times is impractical because of the highly variable clinical course of patients with ARDS. PMID:16539706

  14. Compatibility and stability of palonosetron hydrochloride with four neruomuscular blocking agents during simulated y-site administration.

    PubMed

    Trusley, Craig; Ben, Michael; Kupiec, Thomas C; Trissel, Lawrence A

    2008-01-01

    Palonosetron hydrochloride is a longer-acting selective 5-HT3 receptor antagonist that has been approved for the prevention of chemotherapy-induced nausea and vomiting and is being evaluated for the prevention of postoperative nausea and vomiting. The objective of this study was to evaluate the physical and chemical stability of palonosetron hydrochloride 50 mcg/mL when mixed with any of the neuromuscular blocking drugs cisatracurium besylate 0.5 mg/mL, rocuronium bromide 1 mg/mL, succinylcholine chloride 2 mg/mL, and vecuronium bromide 1 mg/mL during simulated Y-site administration. Triplicate samples of palonosetron hydrochloride with each of the neuromuscular blocking drugs were tested. Samples were stored and evaluated for up to 4 hours at room temperature. Physical stability was assessed by turbidimetric and particulate measurements and visual inspection. Chemical stability was assessed by high-performnace liquid chromatography. All of the admixtures were clear and colorless when viewed in normal fluorescent room light and when viewed with a Tyndall beam. Measured turbidity and particulate content were low initially and remained low throughout the study. The drug concentration was unchanged in all of the samples tested. Palonosetron hydrochloride is physically and chemically stable with cisatracurium besylate, rocuronium bromide, succinylcholine chloride, or vecuronium bromide at the concentrations tested during simulated Y-site administration over 4 hours at ambient room temperature. PMID:23969608

  15. The effect of rocuronium and sugammadex on neuromuscular blockade in a child with congenital myotonic dystrophy type 1.

    PubMed

    Pickard, Amelia; Lobo, Clinton; Stoddart, Peter A

    2013-09-01

    Myotonic dystrophy type 1 (MD1) is the commonest muscular dystrophy found in adults; however, it may present in the neonatal period with hypotonia, talipes, poor feeding, and respiratory failure. Inheritance is autosomal dominant with a defect in the DMPK gene found on the long arm of chromosome 19 with variable expansion of the cytosine-thymine-guanine (CTG) triplet repeat. A 14-month-old boy with congenital MD type 1 was scheduled for percutaneous endoscopic gastrostomy (PEG) insertion, orchidopexy, and division of tongue-tie. Following induction of anesthesia, acceleromyography was used to monitor neuromuscular function. This revealed a very rapid onset of profound neuromuscular block which lasted significantly longer than would be expected in a child without MD1. Sugammadex reversed the block rapidly. The anesthetic management of children with MD1 has been well described but not the acceleromyographic monitored use of rocuronium and its subsequent reversal with the new cyclodextrin sugammadex. PMID:23763618

  16. Rapid synthesis of acetylcholine receptors at neuromuscular junctions. (Reannouncement with new availability information)

    SciTech Connect

    Ramsay, D.A.; Drachman, D.B.; Pestronk, A.

    1988-12-31

    The rate of acetylcholine receptor (AChR) degradation in mature, innervated mammalian neuromuscular junctions has recently been shown to be biphasic; up to 20% are rapidly turned over whereas the remainder are lost more slowly. In order to maintain normal junctional receptor density, synthesis and insertion of AChRs should presumably be sufficiently rapid to replace both the RTOs and the stable receptors. The authors have tested this prediction by blocking pre-existing AChRs in the mouse sternomastoid muscle with alpha bungarotoxin and monitoring the subsequent appearance of new junctional AChRs at intervals of 3 h to 20 days by labelling them. The results show that new receptors were initially inserted rapidly. The rate of increase of new binding sites gradually slowed down during the remainder of the time period studied. Control observations excluded possible artifacts of the experimental procedure including incomplete blockade of AChRs, dissociation of toxin receptor complexes, or experimentally induced alteration of receptor synthesis. The present demonstration of rapid synthesis and incorporation of AChRs at innervated neuromuscular junctions provides support for the concept of a subpopulation of rapidly turned over AChRs. The RTOs may serve as precursors for the large population of stable receptors and have an important role in the metabolism of the neuromuscular synapse.

  17. Studies on neuromuscular blockade by boldine in the mouse phrenic nerve-diaphragm.

    PubMed

    Kang, J J; Cheng, Y W; Fu, W M

    1998-02-01

    The effects of boldine [(S)-2,9-dihydroxyl-1,10-dimethoxy-aporphine], a major alkaloid in the leaves and bark of Boldo (Peumus boldus Mol.), on neuromuscular transmission were studied using a muscle phrenic-nerve diaphragm preparation. Boldine at concentrations lower than 200 microM preferentially inhibited, after an initial period of twitch augmentation, the nerve-evoked twitches of the mouse diaphragm and left the muscle-evoked twitches unaffected. The twitch inhibition could be restored by neostigmine or washout with Krebs solution. The twitches evoked indirectly and directly were both augmented initially, suggesting that the twitch augmentation induced by boldine was myogenic. Boldine inhibited the acetylcholine-induced contraction of denervated diaphragm dose-dependently with an IC50 value of 13.5 microM. At 50 microM, boldine specifically inhibited the amplitude of the miniature end plate potential. In addition, boldine was similar to d-tubocurarine in its action to reverse the neuromuscular blocking action of alpha-bungarotoxin. These results showed that the neuromuscular blockade by boldine on isolated mouse phrenic-nerve diaphragm might be due to its direct interaction with the postsynaptic nicotinic acetylcholine receptor. PMID:9541284

  18. Neuromuscular Effects of Common Krait (Bungarus caeruleus) Envenoming in Sri Lanka

    PubMed Central

    Silva, Anjana; Maduwage, Kalana; Sedgwick, Michael; Pilapitiya, Senaka; Weerawansa, Prasanna; Dahanayaka, Niroshana J.; Buckley, Nicholas A.; Johnston, Christopher; Siribaddana, Sisira; Isbister, Geoffrey K.

    2016-01-01

    Objective We aimed to investigate neurophysiological and clinical effects of common krait envenoming, including the time course and treatment response. Methodology Patients with definite common krait (Bungarus caeruleus) bites were recruited from a Sri Lankan hospital. All patients had serial neurological examinations and stimulated concentric needle single-fibre electromyography (sfEMG) of orbicularis oculi in hospital at 6wk and 6–9mth post-bite. Principal Findings There were 33 patients enrolled (median age 35y; 24 males). Eight did not develop neurotoxicity and had normal sfEMG. Eight had mild neurotoxicity with ptosis, normal sfEMG; six received antivenom and all recovered within 20–32h. Seventeen patients developed severe neurotoxicity with rapidly descending paralysis, from ptosis to complete ophthalmoplegia, facial, bulbar and neck weakness. All 17 received Indian polyvalent antivenom a median 3.5h post-bite (2.8–7.2h), which cleared unbound venom from blood. Despite this, the paralysis worsened requiring intubation and ventilation within 7h post-bite. sfEMG showed markedly increased jitter and neuromuscular blocks within 12h. sfEMG abnormalities gradually improved over 24h, corresponding with clinical recovery. Muscle recovery occurred in ascending order. Myotoxicity was not evident, clinically or biochemically, in any of the patients. Patients were extubated a median 96h post-bite (54–216h). On discharge, median 8 days (4–12days) post-bite, patients were clinically normal but had mild sfEMG abnormalities which persisted at 6wk post-bite. There were no clinical or neurophysiological abnormalities at 6–9mth. Conclusions Common krait envenoming causes rapid onset severe neuromuscular paralysis which takes days to recover clinically consistent with sfEMG. Subclinical neuromuscular dysfunction lasts weeks but was not permanent. Antivenom effectively cleared venom but did not prevent worsening or reverse neuromuscular paralysis. PMID:26829229

  19. Neuromuscular adaptations during submaximal prolonged cycling.

    PubMed

    Castronovo, A M; De Marchis, C; Bibbo, D; Conforto, S; Schmid, M; D'Alessio, T

    2012-01-01

    This study aims at evaluating the neuromuscular adaptations occurring during submaximal prolonged cycling tasks. In particular, we want to assess changes in surface electromyographic (sEMG) signal recorded during a pedaling task, performed by six subjects on a cycle-simulator at a constant power output, until voluntary exhaustion. Task failure was defined as the instant the subject was no longer able to maintain the required task. Electromyographic activity was recorded from eight muscles of the dominant leg and burst characteristics of sEMG signals were analyzed in order to assess the changes in muscle activity level produced by the occurrence of neuromuscular fatigue. In particular, three features were extracted from the sEMG signal for each burst: amplitude, location of the maxima and mean profile of the burst envelope. We have reported an increase in the amplitude parameter for all subjects only for Vastii while bi-articular muscles presented a high variability among subjects. Also the location of the maximal values of the mean envelope of the bursts was found to change when considering bi-articular or mono-articular muscles. The envelope profile was found not to be subject to alterations when comparing the end of the task with the beginning. We speculated that neuromuscular fatigue induces changes essentially in the mono-articular muscles which produce power. This phenomenon is highly correlated with the adopted pedaling strategy which, being not constrained, induces subjects to express the maximal power in the downstroke phase, related to knee extension and involving mainly mono-articular muscles. PMID:23366709

  20. Neuromuscular Functions on Experimental Acute Methanol Intoxication

    PubMed Central

    Moral, Ali Reşat; Çankayalı, İlkin; Sergin, Demet; Boyacılar, Özden

    2015-01-01

    Objective The incidence of accidental or suicidal ingestion of methyl alcohol is high and methyl alcohol intoxication has high mortality. Methyl alcohol intoxication causes severe neurological sequelae and appears to be a significant problem. Methyl alcohol causes acute metabolic acidosis, optic neuropathy leading to permanent blindness, respiratory failure, circulatory failure and death. It is metabolised in the liver, and its metabolite formic acid has direct toxic effects, causing oxidative stress, mitochondrial damage and increased lipid peroxidation associated with the mechanism of neurotoxicity. Methanol is known to cause acute toxicity of the central nervous system; however, the effects on peripheral neuromuscular transmission are unknown. In our study, we aimed to investigate the electrophysiological effects of experimentally induced acute methanol intoxication on neuromuscular transmission in the early period (first 24 h). Methods After approval by the Animal Experiment Ethics Committee of Ege University, the study was carried out on 10 Wistar rats, each weighing about 200 g. During electrophysiological recordings and orogastric tube insertion, the rats were anaesthetised using intra-peritoneal (IP) injection of ketamine 100 mg kg−1 and IP injection of xylazine 10 mg kg−1. The rats were given 3 g kg−1 methyl alcohol by the orogastric tube. Electrophysiological measurements from the gastrocnemius muscle were compared with baseline. Results Latency measurements before and 24 h after methanol injection were 0.81±0.11 ms and 0.76±0.12 ms, respectively. CMAP amplitude measurements before and 24 h after methanol injection were 9.85±0.98 mV and 9.99±0.40 mV, respectively. CMAP duration measurements before and 24 h after methanol injection were 9.86±0.03 ms and 9.86±0.045 ms, respectively. Conclusion It was concluded that experimental methanol intoxication in the acute phase (first 24 h) did not affect neuromuscular function. PMID:27366524

  1. Neuromuscular Development and Regulation of Myosin Expression

    NASA Technical Reports Server (NTRS)

    Bodine, Sue

    1997-01-01

    The proposed experiments were designed to determine whether the absence of gravity during embryogenesis influences the postnatal development of the neuromuscular system. Further, we examined the effects of reduced gravity on hindlimb muscles of the pregnant rats. Microgravity may have short and long-term effects on the development of muscle fiber type differentiation and force producing capabilities. Microgravity will reduce muscle fiber size and cause a shift in myosin heavy chain expression from slow to fast in hindlimb muscles of the adult pregnant rats.

  2. 21 CFR 882.5810 - External functional neuromuscular stimulator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false External functional neuromuscular stimulator. 882.5810 Section 882.5810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... External functional neuromuscular stimulator. (a) Identification. An external functional...

  3. 21 CFR 882.5810 - External functional neuromuscular stimulator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false External functional neuromuscular stimulator. 882.5810 Section 882.5810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... External functional neuromuscular stimulator. (a) Identification. An external functional...

  4. Motoneuron and sensory neuron plasticity to varying neuromuscular activity levels

    NASA Technical Reports Server (NTRS)

    Ishihara, Akihiko; Roy, Roland R.; Ohira, Yoshinobu; Edgerton, V. Reggie

    2002-01-01

    The size and phenotypic properties of the neural and muscular elements of the neuromuscular unit are matched under normal conditions. When subjected to chronic decreases or increases in neuromuscular activity, however, the adaptations in these properties are much more limited in the neural compared with the muscular elements.

  5. Stress in Families of Children With Neuromuscular Disease.

    ERIC Educational Resources Information Center

    Holroyd, Jean; Guthrie, Donald

    1979-01-01

    This study compared parents of children with neuromuscular diseases to parents of children with psychiatric diagnoses, using the Questionnaire on Resources and Stress. The groups showed different patterns of stress relating to child care. Within the neuromuscular group, parental stress increased with the severity of the child's illness.…

  6. Recent achievements in restorative neurology: Progressive neuromuscular diseases

    SciTech Connect

    Dimitrijevic, M.R.; Kakulas, B.A.; Vrbova, G.

    1986-01-01

    This book contains 27 chapters. Some of the chapter titles are: Computed Tomography of Muscles in Neuromuscular Disease; Mapping the Genes for Muscular Dystrophy; Trophic Factors and Motor Neuron Development; Size of Motor Units and Firing Rate in Muscular Dystrophy; Restorative Possibilities in Relation to the Pathology of Progressive Neuromuscular Disease; and An Approach to the Pathogenesis of some Congenital Myopathies.

  7. Neuromuscular Characteristics of Endurance--And Power-Trained Athletes

    ERIC Educational Resources Information Center

    Koceja, David M.; Davison, Edwin; Robertson, Christopher T.

    2004-01-01

    In response to chronic physical training, the human neuromuscular system undergoes significant and specific adaptations. More importantly, these influences are the result of the type and quantity of physical activity. One of the simplest neuromuscular mechanisms is the spinal stretch reflex. The reflex system was previously viewed as inflexible,…

  8. Protease inhibitor homologues from mamba venoms: facilitation of acetylcholine release and interactions with prejunctional blocking toxins.

    PubMed

    Harvey, A L; Karlsson, E

    1982-09-01

    1 Five polypeptides, which were isolated from elapid snake venoms and which are structurally related to protease inhibitors, were tested for action on isolated biventer cervicis nerve-muscle preparations of the chick. 2 Dendrotoxin from the Eastern green mamba (Dendroaspis angusticeps) and toxins K and I from the black mamba (Dendroaspis polylepis polylepis) increased to indirect stimulation without affecting responses to exogenous acetylcholine, carbachol of KCl. 3 The two other protease inhibitor homologues, HHV-II from Ringhals cobra (Hemachatus haemachatus) and NNV-II from Cape cobra (Naja nivea) did not increase responses to nerve stimulation. Trypsin inhibitor from bovine pancreas also had no facilitatory effects on neuromuscular transmission. 4 The facilitatory toxins from mamba venoms interacted with the prejunctional blocking toxins, beta-bungarotoxin, crotoxin and notexin, but not with taipoxin. The blocking effects of beta-bungarotoxin were reduced by pretreatment with the mamba toxins, whereas the blocking actions of crotoxin and notexin were enhanced. 5 The results indicate that protease inhibitor homologues from mamba venoms form a new class of neurotoxin, which acts to increase the release of acetylcholine in response to motor nerve stimulation. 6 From the interaction studies it is concluded that the facilitatory toxins bind to motor nerve terminals at sites related to those occupied by the prejunctional blocking toxins. However, differences in interactions with individual toxins suggest that there must be several related binding sites on the nerve terminals. PMID:6751453

  9. Electrophysiological study in neuromuscular junction disorders.

    PubMed

    Cherian, Ajith; Baheti, Neeraj N; Iype, Thomas

    2013-01-01

    This review is on ultrastructure and subcellular physiology at normal and abnormal neuromuscular junctions. The clinical and electrophysiological findings in myasthenia gravis, Lambert-Eaton myasthenic syndrome (LEMS), congenital myasthenic syndromes, and botulinum intoxication are discussed. Single fiber electromyography (SFEMG) helps to explain the basis of testing neuromuscular junction function by repetitive nerve stimulation (RNS). SFEMG requires skill and patience and its availability is limited to a few centers. For RNS supramaximal stimulation is essential and so is display of the whole waveform of each muscle response at maximum amplitude. The amplitudes of the negative phase of the first and fourth responses are measured from baseline to negative peak, and the percent change of the fourth response compared with the first represents the decrement or increment. A decrement greater than 10% is accepted as abnormal and smooth progression of response amplitude train and reproducibility form the crux. In suspected LEMS the effect of fast rates of stimulation should be determined after RNS response to slow rates of stimulation. Caution is required to avoid misinterpretation of potentiation and pseudofacilitation. PMID:23661960

  10. Neuromuscular disruption with ultrashort electrical pulses

    NASA Astrophysics Data System (ADS)

    Pakhomov, Andrei; Kolb, Juergen F.; Joshi, Ravindra P.; Schoenbach, Karl H.; Dayton, Thomas; Comeaux, James; Ashmore, John; Beason, Charles

    2006-05-01

    Experimental studies on single cells have shown that application of pulsed voltages, with submicrosecond pulse duration and an electric field on the order of 10 kV/cm, causes sudden alterations in the intracellular free calcium concentration, followed by immobilization of the cell. In order to examine electrical stimulation and incapacitation with such ultrashort pulses, experiments on anesthetized rats have been performed. The effect of single, 450 nanosecond monopolar pulses have been compared with that of single pulses with multi-microsecond duration (TASER pulses). Two conditions were explored: 1. the ability to elicit a muscle twitch, and, 2. the ability to suppress voluntary movement by using nanosecond pulses. The second condition is relevant for neuromuscular incapacitation. The preliminary results indicate that for stimulation microsecond pulses are advantageous over nanosecond pulses, whereas for incapacitation, the opposite seems to apply. The stimulation effects seem to scale with electrical charge, whereas the disruption effects don't follow a simple scaling law. The increase in intensity (time of incapacitation) for a given pulse duration, is increasing with electrical energy, but is more efficient for nanosecond than for microsecond pulses. This indicates different cellular mechanisms for incapacitation, most likely subcellular processes, which have been shown to become increasingly important when the pulse duration is shortened into the nanosecond range. If further studies can confirm these initial results, consequences of reduced pulse duration are a reduction in weight and volume of the pulse delivery system, and likely, because of the lower required energy for neuromuscular incapacitation, reduced safety risks.

  11. Mechanism of neuromuscular dysfunction in Krabbe disease.

    PubMed

    Cantuti-Castelvetri, Ludovico; Maravilla, Erick; Marshall, Michael; Tamayo, Tammy; D'auria, Ludovic; Monge, John; Jeffries, James; Sural-Fehr, Tuba; Lopez-Rosas, Aurora; Li, Guannan; Garcia, Kelly; van Breemen, Richard; Vite, Charles; Garcia, Jesus; Bongarzone, Ernesto R

    2015-01-28

    The atrophy of skeletal muscles in patients with Krabbe disease is a major debilitating manifestation that worsens their quality of life and limits the clinical efficacy of current therapies. The pathogenic mechanism triggering muscle wasting is unknown. This study examined structural, functional, and metabolic changes conducive to muscle degeneration in Krabbe disease using the murine (twitcher mouse) and canine [globoid cell leukodystrophy (GLD) dog] models. Muscle degeneration, denervation, neuromuscular [neuromuscular junction (NMJ)] abnormalities, and axonal death were investigated using the reporter transgenic twitcher-Thy1.1-yellow fluorescent protein mouse. We found that mutant muscles had significant numbers of smaller-sized muscle fibers, without signs of regeneration. Muscle growth was slow and weak in twitcher mice, with decreased maximum force. The NMJ had significant levels of activated caspase-3 but limited denervation. Mutant NMJ showed reduced surface areas and lower volumes of presynaptic terminals, with depressed nerve control, increased miniature endplate potential (MEPP) amplitude, decreased MEPP frequency, and increased rise and decay rate constants. Twitcher and GLD dog muscles had significant capacity to store psychosine, the neurotoxin that accumulates in Krabbe disease. Mechanistically, muscle defects involved the inactivation of the Akt pathway and activation of the proteasome pathway. Our work indicates that muscular dysfunction in Krabbe disease is compounded by a pathogenic mechanism involving at least the failure of NMJ function, activation of proteosome degradation, and a reduction of the Akt pathway. Akt, which is key for muscle function, may constitute a novel target to complement in therapies for Krabbe disease. PMID:25632136

  12. Neuromuscular Dysfunction in Experimental Sepsis and Glutamine

    PubMed Central

    Çankayalı, İlkin; Boyacılar, Özden; Demirağ, Kubilay; Uyar, Mehmet; Moral, Ali Reşat

    2016-01-01

    Background: Electrophysiological studies show that critical illness polyneuromyopathy appears in the early stage of sepsis before the manifestation of clinical findings. The metabolic response observed during sepsis causes glutamine to become a relative essential amino acid. Aims: We aimed to assess the changes in neuromuscular transmission in the early stage of sepsis after glutamine supplementation. Study Design: Animal experimentation. Methods: Twenty male Sprague-Dawley rats were randomized into two groups. Rats in both groups were given normal feeding for one week. In the study group, 1 g/kg/day glutamine was added to normal feeding by feeding tube for one week. Cecal ligation and perforation (CLP) surgery was performed at the end of one week. Before and 24 hours after CLP, compound muscle action potentials were recorded from the gastrocnemius muscle. Results: Latency measurements before and 24 hours after CLP were 0.68±0.05 ms and 0.80±0.09 ms in the control group and 0.69±0.07 ms and 0.73±0.07 ms in the study group (p<0.05). Conclusion: Since enteral glutamine prevented compound muscle action potentials (CMAP) latency prolongation in the early phase of sepsis, it was concluded that enteral glutamine replacement might be promising in the prevention of neuromuscular dysfunction in sepsis; however, further studies are required. PMID:27308070

  13. Neuromuscular imaging in inherited muscle diseases

    PubMed Central

    Kley, Rudolf A.; Fischer, Dirk

    2010-01-01

    Driven by increasing numbers of newly identified genetic defects and new insights into the field of inherited muscle diseases, neuromuscular imaging in general and magnetic resonance imaging (MRI) in particular are increasingly being used to characterise the severity and pattern of muscle involvement. Although muscle biopsy is still the gold standard for the establishment of the definitive diagnosis, muscular imaging is an important diagnostic tool for the detection and quantification of dystrophic changes during the clinical workup of patients with hereditary muscle diseases. MRI is frequently used to describe muscle involvement patterns, which aids in narrowing of the differential diagnosis and distinguishing between dystrophic and non-dystrophic diseases. Recent work has demonstrated the usefulness of muscle imaging for the detection of specific congenital myopathies, mainly for the identification of the underlying genetic defect in core and centronuclear myopathies. Muscle imaging demonstrates characteristic patterns, which can be helpful for the differentiation of individual limb girdle muscular dystrophies. The aim of this review is to give a comprehensive overview of current methods and applications as well as future perspectives in the field of neuromuscular imaging in inherited muscle diseases. We also provide diagnostic algorithms that might guide us through the differential diagnosis in hereditary myopathies. PMID:20422195

  14. LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction.

    PubMed

    Weatherbee, Scott D; Anderson, Kathryn V; Niswander, Lee A

    2006-12-01

    Low-density lipoprotein receptor-related protein 4 (Lrp4) is a member of a family of structurally related, single-pass transmembrane proteins that carry out a variety of functions in development and physiology, including signal transduction and receptor-mediated endocytosis. Lrp4 is expressed in multiple tissues in the mouse, and is important for the proper development and morphogenesis of limbs, ectodermal organs, lungs and kidneys. We show that Lrp4 is also expressed in the post-synaptic endplate region of muscles and is required to form neuromuscular synapses. Lrp4-mutant mice die at birth with defects in both presynaptic and postsynaptic differentiation, including aberrant motor axon growth and branching, a lack of acetylcholine receptor and postsynaptic protein clustering, and a failure to express postsynaptic genes selectively by myofiber synaptic nuclei. Our data show that Lrp4 is required during the earliest events in postsynaptic neuromuscular junction (NMJ) formation and suggest that it acts in the early, nerveindependent steps of NMJ assembly. The identification of Lrp4 as a crucial factor for NMJ formation may have implications for human neuromuscular diseases such as myasthenia syndromes. PMID:17119023

  15. A CC' loop decoy peptide blocks the interaction between Act1 and IL-17RA to attenuate IL-17- and IL-25-induced inflammation.

    PubMed

    Liu, Caini; Swaidani, Shadi; Qian, Wen; Kang, Zizhen; Sun, Paige; Han, Yue; Wang, Chenhui; Gulen, Muhammet Fatih; Yin, Weiguo; Zhang, Chunjiang; Fox, Paul L; Aronica, Mark; Hamilton, Thomas A; Misra, Saurav; Deng, Junpeng; Li, Xiaoxia

    2011-01-01

    Interleukin-17 (IL-17) and IL-25 signaling induce the expression of genes encoding inflammatory factors and are implicated in the pathology of various inflammatory diseases. Nuclear factor κB (NF-κB) activator 1 (Act1) is an adaptor protein and E3 ubiquitin ligase that is critical for signaling by either IL-17 or IL-25, and it is recruited to their receptors (IL-17R and IL-25R) through heterotypic interactions between the SEFIR [SEF (similar expression to fibroblast growth factor genes) and IL-17R] domain of Act1 and that of the receptor. SEFIR domains have structural similarity with the Toll-IL-1 receptor (TIR) domains of Toll-like receptors and IL-1R. Whereas the BB' loop of TIR is required for TIR-TIR interactions, we found that deletion of the BB' loop from Act1 or IL-17RA (a common subunit of both IL-17R and IL-25R) did not affect Act1-IL-17RA interactions; rather, deletion of the CC' loop from Act1 or IL-17RA abolished the interaction between both proteins. Surface plasmon resonance measurements showed that a peptide corresponding to the CC' loop of Act1 bound directly to IL-17RA. A cell-permeable decoy peptide based on the CC' loop sequence inhibited IL-17- or IL-25-mediated signaling in vitro, as well as IL-17- and IL-25-induced pulmonary inflammation in mice. Together, these findings provide the molecular basis for the specificity of SEFIR-SEFIR versus TIR-TIR domain interactions and consequent signaling. Moreover, we suggest that the CC' loop motif of SEFIR domains is a promising target for therapeutic strategies against inflammatory diseases associated with IL-17 or IL-25 signaling. PMID:22045852

  16. Activity-dependent degeneration of axotomized neuromuscular synapses in WldS mice

    PubMed Central

    Brown, R.; Hynes-Allen, A.; Swan, A.J.; Dissanayake, K.N.; Gillingwater, T.H.; Ribchester, R.R.

    2015-01-01

    Activity and disuse of synapses are thought to influence progression of several neurodegenerative diseases in which synaptic degeneration is an early sign. Here we tested whether stimulation or disuse renders neuromuscular synapses more or less vulnerable to degeneration, using axotomy as a robust trigger. We took advantage of the slow synaptic degeneration phenotype of axotomized neuromuscular junctions in flexor digitorum brevis (FDB) and deep lumbrical (DL) muscles of Wallerian degeneration-Slow (WldS) mutant mice. First, we maintained ex vivo FDB and DL nerve-muscle explants at 32 °C for up to 48 h. About 90% of fibers from WldS mice remained innervated, compared with about 36% in wild-type muscles at the 24-h checkpoint. Periodic high-frequency nerve stimulation (100 Hz: 1 s/100 s) reduced synaptic protection in WldS preparations by about 50%. This effect was abolished in reduced Ca2+ solutions. Next, we assayed FDB and DL innervation after 7 days of complete tetrodotoxin (TTX)-block of sciatic nerve conduction in vivo, followed by tibial nerve axotomy. Five days later, only about 9% of motor endplates remained innervated in the paralyzed muscles, compared with about 50% in 5 day-axotomized muscles from saline-control-treated WldS mice with no conditioning nerve block. Finally, we gave mice access to running wheels for up to 4 weeks prior to axotomy. Surprisingly, exercising WldS mice ad libitum for 4 weeks increased about twofold the amount of subsequent axotomy-induced synaptic degeneration. Together, the data suggest that vulnerability of mature neuromuscular synapses to axotomy, a potent neurodegenerative trigger, may be enhanced bimodally, either by disuse or by hyperactivity. PMID:25617654

  17. Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons

    PubMed Central

    Lee, Young il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

    2011-01-01

    A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precedes the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any significant impairment in neuromuscular transmission, even when animals were maintained up to 5 days longer via a supplementary diet. However, the muscles were clearly weaker, generating less than half their normal tension. Weakness in 3 muscles examined in the study appears due to a severe but uniform reduction in muscle fiber size. The size reduction results from a failure of muscle fibers to grow during early postnatal development and, in soleus, to a reduction in number of fibers generated. Neuromuscular development is severely delayed in these mutant animals: expression of myosin heavy chain isoforms, the elimination of polyneuronal innervation, the maturation in the shape of the AChR plaque, the arrival of SCs at the junctions and their coverage of the nerve terminal, the development of junctional folds. Thus, if SMA in this particular mouse is a disease of motor neurons, it can act in a manner that does not result in their death or disconnection from their targets but nonetheless alters many aspects of neuromuscular development. PMID:21658376

  18. Surgical advances in the treatment of neuromuscular scoliosis

    PubMed Central

    Canavese, Federico; Rousset, Marie; Le Gledic, Benoit; Samba, Antoine; Dimeglio, Alain

    2014-01-01

    Neuromuscular disorders are a group of diseases affecting the neuro-musculo-skeletal system. Children with neuromuscular disorders frequently develop progressive spinal deformities with cardio-respiratory compromise in the most severe cases. The incidence of neuromuscular scoliosis is variable, inversely correlated with ambulatory abilities and with a reported risk ranging from 80% to 100% in non-ambulatory patients. As surgical and peri-operative techniques have improved, more severely affected children with complex neuromuscular deformities and considerable co-morbidities are now believed to be candidates for extensive surgery for spinal deformity. This article aimed to provide a comprehensive review of how neuromuscular spinal deformities can affect normal spine balance and how these deformities can be treated with segmental instrumentation and sub-laminar devices. Older concepts have been integrated with newer scientific data to provide the reader with a basis for better understanding of how treatment of neuromuscular scoliosis has evolved over the past few decades. Recent advances, as well as challenges that remain to be overcome, in the surgical treatment of neuromuscular curves with sub-laminar devices and in the management of post-operative infections are outlined. PMID:24829875

  19. A short, highly repetitive element in intron -1 of the human c-Ha-ras gene acts as a block to transcriptional readthrough by a viral promoter.

    PubMed Central

    Lowndes, N F; Bushel, P; Mendelsohn, L; Wu, J; Yen, M Y; Allan, M

    1990-01-01

    We have identified a short, highly repetitive element within intron -1 of the human c-Ha-ras gene. This element was found to be transcribed in both orientations and to be homologous to heterogeneous nonpolyadenylated transcripts. The repetitive element blocked transcriptional readthrough from a strong upstream viral promoter but allowed unimpaired readthrough from the c-Has-ras promoter. We suggest that it may serve to prevent excessive transcription into the coding region of the gene under such circumstances as viral insertion. Images PMID:2201911

  20. THE ROLE OF THE NEUROMUSCULAR MEDICINE SPECIALIST AND PHYSIATRY IN THE MANAGEMENT OF NEUROMUSCULAR DISEASE

    PubMed Central

    McDonald, Craig M.; Fowler, William M.

    2012-01-01

    Synopsis The neuromuscular medicine, and physiatry specialists are key health care providers who work cooperatively with a multidisciplinary team to provide coordinated care for persons with Neuromuscular diseases (NMDs). The director or coordinator of the team must be aware of the potential issues specific to NMDs and be able to access the interventions that are the foundations for proper care in NMD. These include health maintenance and proper monitoring of disease progression and complications to provide anticipatory, preventive care and optimum management. Ultimate goals include maximizing health and functional capacities, performing medical monitoring and surveillance to inhibit and prevent complications, and promoting access and full integration into the community in order to optimize quality of life. PMID:22938874

  1. A CC′ Loop Decoy Peptide Blocks the Interaction Between Act1 and IL-17RA to Attenuate IL-17- and IL-25-Induced Inflammation

    PubMed Central

    Liu, Caini; Swaidani, Shadi; Qian, Wen; Kang, Zizhen; Sun, Paige; Han, Yue; Wang, Chenhui; Gulen, Muhammet Fatih; Yin, Weiguo; Zhang, Chunjiang; Fox, Paul L; Aronica, Mark; Hamilton, Thomas A; Misra, Saurav; Deng, Junpeng; Li, Xiaoxia

    2012-01-01

    Interleukin-17 (IL-17) and IL-25 signaling induce the expression of genes that encode inflammatory factors and they are implicated in the pathology of various inflammatory diseases. Nuclear factor κB (NF-κB) activator 1 (Act1) is an adaptor protein and E3 ubiquitin ligase that is critical for IL-17 and IL-25 signaling, and it is recruited to their receptors through heterotypic interactions between their SEFIR [SEF (similar expression to fibroblast growth factor genes)/IL-17R] domains. Modeling of SEFIR domains has shown their structural similarity with the Toll-IL-1 receptor (TIR) domains of Toll-like receptors (TLRs) and the IL-1R. Whereas the BB′ loop of TIR is required for TIR-TIR interactions, we found that deletion of the BB′ loop from Act1 or IL-17RA (a common subunit of IL-17R and IL-25R) did not affect Act1–IL-17RA interactions. Instead, deletion of the CC′ loop from Act1 or IL-17RA abolished the interaction between Act1 and IL-17RA, suggesting that SEFIR and TIR domains interact in different manners. Surface plasmon resonance measurements showed that a peptide corresponding to the CC′ loop bound directly to IL-17RA. A cell-permeable decoy peptide based on the CC′ loop sequence inhibited IL-17- and IL-25-mediated signaling, and it inhibited IL-17- and IL-25-induced responses in vitro and pulmonary inflammation in vivo. Together, these findings provide the molecular basis for the specificity of SEFIR versus TIR domain interactions and consequent signaling. Moreover, we suggest that the CC′ loop motif of SEFIR domains is a promising target for therapeutic strategies against IL-17- and IL-25-asssociated inflammatory diseases. PMID:22045852

  2. Population Blocks.

    ERIC Educational Resources Information Center

    Smith, Martin H.

    1992-01-01

    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

  3. Management of Cardiac Involvement in NeuroMuscular Diseases: Review

    PubMed Central

    Bouhouch, Rachida; Elhouari, Tarik; Oukerraj, Latifa; Fellat, Ibtissam; Zarzur, Jamila; Bennani, Rajaa; Arharbi, Mhamed

    2008-01-01

    Neuromuscular Diseases are a heterogeneous molecular, clinical and prognosis group. Progress has been achieved in the understanding and classification of these diseases. Cardiac involvement in neuromuscular diseases namely conduction disorders, ventricular dilatation and dilated cardiomyopathy with its impact on prognosis, is often dissociated from the peripheral myopathy. Therefore, close surveillance is mandatory in the affected patients. In this context, preventive therapy (beta-blockers and angiotensin converting enzyme inhibitors) has been recently recommended in the most common Neuromuscular Diseases, Duchenne Muscular Dystrophy and Myotonic Dystrophy. PMID:19337361

  4. Wnt Signaling in Neuromuscular Junction Development

    PubMed Central

    Koles, Kate

    2012-01-01

    Wnt proteins are best known for their profound roles in cell patterning, because they are required for the embryonic development of all animal species studied to date. Besides regulating cell fate, Wnt proteins are gaining increasing recognition for their roles in nervous system development and function. New studies indicate that multiple positive and negative Wnt signaling pathways take place simultaneously during the formation of vertebrate and invertebrate neuromuscular junctions. Although some Wnts are essential for the formation of NMJs, others appear to play a more modulatory role as part of multiple signaling pathways. Here we review the most recent findings regarding the function of Wnts at the NMJ from both vertebrate and invertebrate model systems. PMID:22510459

  5. Load-dependent regulation of neuromuscular system

    NASA Technical Reports Server (NTRS)

    Ohira, Yoshinobu; Kawano, Fuminori; Stevens, James L.; Wang, Xiao D.; Ishihara, Akihiko

    2004-01-01

    Roles of gravitational loading, sarcomere length, and/or tension development on the electromyogram (EMG) of soleus and afferent neurogram recorded at the L5 segmental level of spinal cord were investigated during parabolic flight of a jet airplane or hindlimb suspension in conscious rats. Both EMG and neurogram levels were increased when the gravity levels were elevated from 1-G to 2-G during the parabolic flight. They were decreased when the hindlimbs were unloaded by exposure to actual microgravity or by suspension. These phenomena were related to passive shortening of muscle fibers and/or sarcomeres. Unloading-related decrease in sarcomere length was greater at the central rather than the proximal and distal regions of fibers. These activities and tension development were not detected when the mean sarcomere length was less than 2.03 micrometers. It is suggested that load-dependent regulation of neuromuscular system is related to the tension development which is influenced by sarcomere length.

  6. Neuromuscular synaptogenesis: coordinating partners with multiple functions.

    PubMed

    Darabid, Houssam; Perez-Gonzalez, Anna P; Robitaille, Richard

    2014-11-01

    The formation of highly efficient and reliable synapses at the neuromuscular junction (NMJ) relies on dynamic molecular interactions. Studies of the development and maturation of the NMJ have focused on events that are dependent on synaptic activity and that require the coordinated actions of nerve- and muscle-derived molecules with different targets and effects. More recently, perisynaptic Schwann cells--the glial cells at NMJs--have become an important focus of research. These glia concomitantly contribute to pre- and postsynaptic maturation while undergoing maturation themselves. Thus, an intricate 'danse à trois’'regulates the maturation of the NMJ to form a highly efficient communication unit, in which fine glial processes lie in close proximity to a highly concentrated population of postsynaptic receptors and perfectly aligned presynaptic release sites. PMID:25493308

  7. Mechanism of Neuromuscular Dysfunction in Krabbe Disease

    PubMed Central

    Cantuti-Castelvetri, Ludovico; Maravilla, Erick; Marshall, Michael; Tamayo, Tammy; D'auria, Ludovic; Monge, John; Jeffries, James; Sural-Fehr, Tuba; Lopez-Rosas, Aurora; Li, Guannan; Garcia, Kelly; van Breemen, Richard; Vite, Charles; Garcia, Jesus

    2015-01-01

    The atrophy of skeletal muscles in patients with Krabbe disease is a major debilitating manifestation that worsens their quality of life and limits the clinical efficacy of current therapies. The pathogenic mechanism triggering muscle wasting is unknown. This study examined structural, functional, and metabolic changes conducive to muscle degeneration in Krabbe disease using the murine (twitcher mouse) and canine [globoid cell leukodystrophy (GLD) dog] models. Muscle degeneration, denervation, neuromuscular [neuromuscular junction (NMJ)] abnormalities, and axonal death were investigated using the reporter transgenic twitcher–Thy1.1–yellow fluorescent protein mouse. We found that mutant muscles had significant numbers of smaller-sized muscle fibers, without signs of regeneration. Muscle growth was slow and weak in twitcher mice, with decreased maximum force. The NMJ had significant levels of activated caspase-3 but limited denervation. Mutant NMJ showed reduced surface areas and lower volumes of presynaptic terminals, with depressed nerve control, increased miniature endplate potential (MEPP) amplitude, decreased MEPP frequency, and increased rise and decay rate constants. Twitcher and GLD dog muscles had significant capacity to store psychosine, the neurotoxin that accumulates in Krabbe disease. Mechanistically, muscle defects involved the inactivation of the Akt pathway and activation of the proteasome pathway. Our work indicates that muscular dysfunction in Krabbe disease is compounded by a pathogenic mechanism involving at least the failure of NMJ function, activation of proteosome degradation, and a reduction of the Akt pathway. Akt, which is key for muscle function, may constitute a novel target to complement in therapies for Krabbe disease. PMID:25632136

  8. Cardiorespiratory and neuromuscular responses to motocross riding.

    PubMed

    Konttinen, Tomi; Kyröläinen, Heikki; Häkkinen, Keijo

    2008-01-01

    The aim of the present study was to examine physiological and neuromuscular responses during motocross riding at individual maximal speed together with the riding-induced changes in maximal isometric force production. Seven A-level (group A) and 5 hobby-class (group H) motocross-riders performed a 30-minute riding test on a motocross track and maximal muscle strength and oxygen uptake (VO2max) tests in a laboratory. During the riding the mean (+/-SD) VO2 reduced in group A from 86 +/- 10% to 69 +/- 6% of the maximum (P < 0.001), whereas in group H the corresponding reduction was from 94 +/- 25% to 82 +/- 20% (P < 0.05). This relative VO2 during the riding correlated with riding speed (r = 0.70, P < 0.01). Heart rate (HR) was maintained at the level of 97 +/- 7% of its maximum in group A and at 98 +/- 3% in group H. Mean muscle activation of the lower body during riding varied between 24% and 38% of its maximum in group A and between 40% and 45% in group H. In conclusion, motocross is a sport that causes great physical stress and demands on both skill and physical capacity of the rider. Physical stress occurs as the result of handling of the bike when receiving continuous impacts in the situation requiring both aerobic and anaerobic metabolism. Our data suggest that both maximal capacity and strain during the ride should be measured to analyze the true physiological and neuromuscular demands of motocross ride. For the practice, this study strongly suggests to train not only aerobic and anaerobic capacity but also to use strength and power training for successful motocross riding. PMID:18296976

  9. Neuromuscular impairment following backpack load carriage.

    PubMed

    Blacker, Sam D; Fallowfield, Joanne L; Bilzon, James L J; Willems, Mark E T

    2013-01-01

    Load Carriage using backpacks is an occupational task and can be a recreational pursuit. The aim of this study was to investigate the mechanisms responsible for changes in neuromuscular function of the m. quadriceps femoris following load carriage. The physiological responses of 10 male participants to voluntary and electrically stimulated isometric contractions were measured before and immediately after two hours of treadmill walking at 6.5 km•h(-1) during level walking with no load [LW], and level walking with load carriage (25 kg backpack) [LC]. Maximal voluntary contraction force decreased by 15 ± 11 % following LC (p=0.006), with no change following LW (p=0.292). Voluntary activation decreased after LW and LC (p=0.033) with no difference between conditions (p=0.405). Doublet contraction time decreased after both LW and LC (p=0.002), with no difference between conditions (p=0.232). There were no other changes in electrically invoked doublet parameters in either condition. The 20:50 Hz ratio did not change following LW (p=0.864) but decreased from 0.88 ± 0.04 to 0.84 ± 0.04 after LC (p=0.011) indicating reduced Ca2+ release from the sarcoplasmic reticulum during excitation contraction coupling. In conclusion, two hours of load carriage carrying a 25 kg back pack caused neuromuscular impairment through a decrease in voluntary activation (i.e. central drive) and fatigue or damage to the peripheral muscle, including impairment of the excitation contraction coupling process. This may reduce physical performance and increase the risk of musculoskeletal injury. PMID:24146709

  10. Neuromuscular Impairment Following Backpack Load Carriage

    PubMed Central

    Blacker, Sam D.; Fallowfield, Joanne L.; Bilzon, James L.J.; Willems, Mark E.T.

    Load Carriage using backpacks is an occupational task and can be a recreational pursuit. The aim of this study was to investigate the mechanisms responsible for changes in neuromuscular function of the m. quadriceps femoris following load carriage. The physiological responses of 10 male participants to voluntary and electrically stimulated isometric contractions were measured before and immediately after two hours of treadmill walking at 6.5 km•h −1 during level walking with no load [LW], and level walking with load carriage (25 kg backpack) [LC]. Maximal voluntary contraction force decreased by 15 ± 11 % following LC (p=0.006), with no change following LW (p=0.292). Voluntary activation decreased after LW and LC (p=0.033) with no difference between conditions (p=0.405). Doublet contraction time decreased after both LW and LC (p=0.002), with no difference between conditions (p=0.232). There were no other changes in electrically invoked doublet parameters in either condition. The 20:50 Hz ratio did not change following LW (p=0.864) but decreased from 0.88 ± 0.04 to 0.84 ± 0.04 after LC (p=0.011) indicating reduced Ca2+ release from the sarcoplasmic reticulum during excitation contraction coupling. In conclusion, two hours of load carriage carrying a 25 kg back pack caused neuromuscular impairment through a decrease in voluntary activation (i.e. central drive) and fatigue or damage to the peripheral muscle, including impairment of the excitation contraction coupling process. This may reduce physical performance and increase the risk of musculoskeletal injury. PMID:24146709

  11. Cotrel-Dubousset instrumentation in neuromuscular scoliosis.

    PubMed

    Piazzolla, Andrea; Solarino, G; De Giorgi, S; Mori, C M; Moretti, L; De Giorgi, G

    2011-05-01

    The study design is retrospective. The aim is to describe our experience about the treatment of patients with neuromuscular scoliosis (NMS) using Cotrel-Dubousset instrumentation. Neuromuscular scoliosis are difficult deformities to treat. A careful assessment and an understanding of the primary disease and its prognosis are essential for planning treatment which is aimed at maximizing function. These patients may have pelvic obliquity, dislocation of the hip, limited balance or ability to sit, back pain, and, in some cases, a serious decrease in pulmonary function. Spinal deformity is difficult to control with a brace, and it may progress even after skeletal maturity has been reached. Surgery is the main stay of treatment for selected patients. The goals of surgery are to correct the deformity producing a balanced spine with a level pelvis and a solid spinal fusion to prevent or delay secondary respiratory complications. The instrumented spinal fusion (ISF) with second-generation instrumentation (e.g., Luque-Galveston and unit rod constructs), are until 1990s considered the gold standard surgical technique for neuromuscular scoliosis (NMS). Still in 2008 Tsirikos et al. said that "the Unit rod instrumentation is a common standard technique and the primary instrumentation system for the treatment of pediatric patients with cerebral palsy and neuromuscular scoliosis because it is simple to use, it is considerably less expensive than most other systems, and can achieve good deformity correction with a low loss of correction, as well as a low prevalence of associated complications and a low reoperation rate." In spite of the Cotrel-Dubousset (CD) surgical technique, used since the beginning of the mid 1980s, being already considered the highest level achieved in correction of scoliosis by a posterior approach, Teli et al., in 2006, said that reports are lacking on the results of third-generation instrumentation for the treatment of NMS. Patients with neuromuscular

  12. Management of Spinal Deformity in Adult Patients With Neuromuscular Disease.

    PubMed

    Protopsaltis, Themistocles S; Boniello, Anthony J; Schwab, Frank J

    2016-09-01

    A wide range of neuromuscular diseases, including Parkinson disease, cerebral palsy, multiple sclerosis, and myopathy, are associated with spinal deformities. The most common postural deformities include anterocollis, Pisa syndrome (pleurothotonus), scoliosis, and camptocormia. Nonsurgical management of spinal deformity in patients with neuromuscular disease centers on maximizing the medical management of the underlying neurodegenerative pathology before surgical intervention is contemplated. Surgical management can include decompression alone, or decompression and fusion with short or long fusion constructs. Patients with neuromuscular disease are susceptible to postoperative medical complications, such as delirium, epidural hematomas, pulmonary emboli, and cardiac events. Compared with outcomes in the typical patient with spinal deformity, postoperative outcomes in patients with neuromuscular disease have higher rates of surgical complications, such as instrumentation failure, proximal junctional kyphosis, loss of correction, and the need for revision surgery, regardless of the magnitude of surgical treatment. PMID:27471900

  13. 21 CFR 882.5860 - Implanted neuromuscular stimulator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Date PMA or notice of completion of PDP is required. A PMA or notice of completion of a PDP for a.... Any other implanted neuromuscular stimulator shall have an approved PMA or declared completed PDP...

  14. 21 CFR 882.5860 - Implanted neuromuscular stimulator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) Date PMA or notice of completion of PDP is required. A PMA or notice of completion of a PDP for a.... Any other implanted neuromuscular stimulator shall have an approved PMA or declared completed PDP...

  15. [Neuromuscular relaxation and CCMDP. The Zilgrei and Feldenkrais methods 2].

    PubMed

    Santoro, F; Maiorana, C; Faccin, C

    1989-10-31

    The Authors show two neuromuscular release methods employed in the treatment of cranio-cervico-mandibular syndrome; these methods work at the place of origin of the pathology resolving the symptoms in different districts of the body. PMID:2701432

  16. Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

    ClinicalTrials.gov

    2015-08-24

    Spinal Muscular Atrophy; Charcot-Marie-Tooth Disease; Muscular Dystrophy; Spinal Muscular Atrophy With Respiratory Distress 1; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Disease; Peroneal Muscular Atrophy; Fragile X Syndrome

  17. Preparing for Emergencies: A Checklist for People with Neuromuscular Diseases

    MedlinePlus

    TORNADO • FLASH FLOOD • EARTHQUAKE • WINTER STORM • HURRICANE • FIRE • HAZARDOUS MATERIALS SPILL Preparing for Emergencies A Checklist for People with Neuromuscular Diseases F or the millions of Americans with limited ...

  18. Improved method for the isolation, characterization and examination of neuromuscular and toxic properties of selected polypeptide fractions from the crude venom of the Taiwan cobra Naja naja atra.

    PubMed

    Ständker, L; Harvey, A L; Fürst, S; Mathes, I; Forssmann, W G; Escalona de Motta, G; Béress, L

    2012-09-15

    An improved chromatographic method was developed to isolate and purify polypeptides and proteins from the crude venom of the Taiwan cobra Naja naja atra. The procedure devised is simple, easy to reproduce, and enables large scale isolation of almost all polypeptides and proteins in this cobra venom. Six pure polypeptide fractions of the venom were isolated and characterized using gel filtration on Sephadex G50 (medium), ion exchange chromatography on SP-Sephadex C25, desalting on Sephadex G25 (fine) and preparative HPLC on a RPC 18 column. The neuromuscular activity of these fractions was tested on the chick biventer cervicis nerve-muscle preparation and their toxicity (LD(50)) was determined after i.v. administration in mice. Their antinociceptive activity was tested in the mouse abdominal test by i.v. application. Two of these polypeptide samples had major physiological effects: one acted as a cardiotoxin causing reversible myocardial contractures with no effect on muscle twitches elicited by nerve stimulation (NS); another was a neurotoxin that blocked muscle contractions in response to NS and exogenously added acetylcholine. The cardiotoxic fraction was identified as CTX I, a well-known cardiotoxin present in this venom, and the neurotoxin was identified as neurotoxin-α with an LD50 in mice of 0.075 mg/kg. PMID:22677803

  19. CLASP2-dependent microtubule capture at the neuromuscular junction membrane requires LL5β and actin for focal delivery of acetylcholine receptor vesicles

    PubMed Central

    Basu, Sreya; Sladecek, Stefan; Martinez de la Peña y Valenzuela, Isabel; Akaaboune, Mohammed; Smal, Ihor; Martin, Katrin; Galjart, Niels; Brenner, Hans Rudolf

    2015-01-01

    A hallmark of the neuromuscular junction (NMJ) is the high density of acetylcholine receptors (AChRs) in the postsynaptic muscle membrane. The postsynaptic apparatus of the NMJ is organized by agrin secreted from motor neurons. The mechanisms that underlie the focal delivery of AChRs to the adult NMJ are not yet understood in detail. We previously showed that microtubule (MT) capture by the plus end–tracking protein CLASP2 regulates AChR density at agrin-induced AChR clusters in cultured myotubes via PI3 kinase acting through GSK3β. Here we show that knockdown of the CLASP2-interaction partner LL5β by RNAi and forced expression of a CLASP2 fragment blocking the CLASP2/LL5β interaction inhibit microtubule capture. The same treatments impair focal vesicle delivery to the clusters. Consistent with these findings, knockdown of LL5β at the NMJ in vivo reduces the density and insertion of AChRs into the postsynaptic membrane. MT capture and focal vesicle delivery to agrin-induced AChR clusters are also inhibited by microtubule- and actin-depolymerizing drugs, invoking both cytoskeletal systems in MT capture and in the fusion of AChR vesicles with the cluster membrane. Combined our data identify a transport system, organized by agrin through PI3 kinase, GSK3β, CLASP2, and LL5β, for precise delivery of AChR vesicles from the subsynaptic nuclei to the overlying synaptic membrane. PMID:25589673

  20. The effects of Duvernoy's gland secretion from the xenodontine colubrid Philodryas olfersii on striated muscle and the neuromuscular junction: partial characterization of a neuromuscular fraction.

    PubMed

    Prado-Franceschi, J; Hyslop, S; Cogo, J C; Andrade, A L; Assakura, M; Cruz-Höfling, M A; Rodrigues-Simioni, L

    1996-04-01

    The effect of Philodryas olfersii Duvernoy's secretion was studied in vivo in mice and chicks as well as in the mouse phrenic nerve-diaphragm and the chick biventer cervicis preparations. The whole secretion (20-40 micrograms/ml) increased the creatine kinase (CK) levels in mice but had no effect on the mouse phrenic nerve-diaphragm preparation. In the chick, the secretion caused head drop and paresia as well as irreversible blockade of the twitch-tension evoked by indirect stimulation in the chick biventer cervicis preparation (50% paralysis in 34.5 +/- 2.7 min, n = 4). The secretion also caused muscle contracture (30% of the maximal twitch-tension generated) after a latency of nearly 9 min. Following fractionation on a Superose 12 FPLC column, the neuromuscular activity was recovered in the high mol. wt fraction (Peak I). At a concentration of 10 micrograms/ml in the chick biventer cervicis preparation, Peak I caused 50% paralysis within 18.5 +/- 3.0 min (n = 4), and evoked a strong contracture (70% of the maximal twitch-tension generated). The contractile responses of the chick preparation to ACh and KCL were partially blocked (90%) by the whole secretion and totally blocked by Peak I. CK release was increased by the whole secretion but not by Peak I. The whole secretion also produced various degrees of muscle cell lysis and extensive widening of the intercellular spaces. The latter showed a loosely arranged membranous network. In general, Peak I caused only minor morphological alterations compared with the whole secretion, although these were still significantly different from those observed in the control preparations. The changes principally involved hypercontraction of the muscle fibers. Based on the above results, we conclude that Peak I contains the factor(s) responsible for the in vitro effects on neuromuscular transmission, whereas the direct myotoxic effect is apparently caused by at least one other component of the Duvernoy's secretion. PMID:8735245

  1. Neuromuscular electrical stimulation for motor relearning in hemiparesis.

    PubMed

    Chae, John

    2003-02-01

    Neuromuscular electrical stimulation may have an important role in improving the motor function of stroke survivors. Active, repetitive movement training mediated by transcutaneous cyclic and EMG-triggered NMES may facilitate the motor recovery of stroke survivors. Multicenter, double-blinded, randomized clinical trials should be pursued to confirm the motor-relearning effects of transcutaneous NMES and to define appropriate prescriptive specifications. Intramuscular EMG-controlled NMES may be superior to transcutaneous systems and is presently undergoing preliminary randomized clinical trials. Neuroprostheses systems may provided the highest level of goal-oriented activity and cognitive investments, which may lead to significant motor relearning. Implementation of clinically viable neuroprosthesis systems, however, will probably require additional technical developments including more reliable control paradigms and methods for blocking undesirable muscle contractions. In view of the dynamic nature of the present health care environment, the future of NMES technology is difficult to predict. By necessity, scientists and clinicians must continue to explore new ideas and to improve on the present systems. Components will be smaller, more durable, and more reliable. Control issues will remain critical for both motor relearning and neuroprosthetic applications, and the implementation of cortical control is likely to dictate the nature of future generations of NMES systems. Finally, consumers will direct future developments. In the present health care environment, where cost has become an overwhelming factor in the development and implementation of new technology, the consumer will become one of technology's greatest advocates. The usual drive toward greater complexity will be tempered by the practical issues of clinical implementation, where patient acceptance is often a function of a tenuous balance between the burden or cost associated with using a system and the

  2. Effects of Pivoting Neuromuscular Training on Pivoting Control and Proprioception

    PubMed Central

    Lee, Song Joo; Ren, Yupeng; Chang, Alison H.; Geiger, François; Zhang, Li-Qun

    2014-01-01

    Purpose Pivoting neuromuscular control and proprioceptive acuity may play an important role in ACL injuries. The goal of this study was to investigate whether pivoting neuromuscular training on an offaxis elliptical trainer (POINT) could improve pivoting neuromuscular control, proprioceptive acuity, and functional performance. Methods Among 41 subjects, 21 subjects participated in 18 sessions of POINT (3 sessions/week for 6 weeks), and 20 subjects served as controls who did their regular workout. Both groups received pre-, mid-, and post-intervention evaluations. Propensity score analysis with multivariable regression adjustment was used to investigate the effect of training on pivoting neuromuscular control (pivoting instability, leg pivoting stiffness, maximum internal and external pivoting angles), proprioceptive acuity, and functional performance in both groups. Results Compared to the control group, the training group significantly improved pivoting neuromuscular control as reduced pivoting instability, reduced maximum internal and external pivoting angles, increased leg pivoting stiffness, and decreased entropy of time to peak EMG in the gluteus maximus and lateral gastrocnemius under pivoting perturbations. Furthermore, the training group enhanced weight-bearing proprioceptive acuity and improved the single leg hop distance. Conclusion Improvement of pivoting neuromuscular control in functional weight-bearing activities and task performances following POINT may help develop lower limb injury prevention and rehabilitation methods to reduce ACL and other musculoskeletal injuries associated with pivoting sports. PMID:24389517

  3. Neuromuscular Fatigue During 200 M Breaststroke

    PubMed Central

    Conceição, Ana; Silva, António J.; Barbosa, Tiago; Karsai, István; Louro, Hugo

    2014-01-01

    The aims of this study were: i) to analyze activation patterns of four upper limb muscles (duration of the active and non-active phase) in each lap of 200m breaststroke, ii) quantify neuromuscular fatigue, with kinematics and physiologic assessment. Surface electromyogram was collected for the biceps brachii, deltoid anterior, pectoralis major and triceps brachii of nine male swimmers performing a maximal 200m breaststroke trial. Swimming speed, SL, SR, SI decreased from the 1st to the 3rd lap. SR increased on the 4th lap (35.91 ± 2.99 stroke·min-1). Peak blood lactate was 13.02 ± 1.72 mmol·l-1 three minutes after the maximal trial. The EMG average rectified value (ARV) increased at the end of the race for all selected muscles, but the deltoid anterior and pectoralis major in the 1st lap and for biceps brachii, deltoid anterior and triceps brachii in the 4th lap. The mean frequency of the power spectral density (MNF) decreased at the 4th lap for all muscles. These findings suggest the occurrence of fatigue at the beginning of the 2nd lap in the 200m breaststroke trial, characterized by changes in kinematic parameters and selective changes in upper limb muscle action. There was a trend towards a non-linear fatigue state. Key Points Fatigue in the upper limbs occurs in different way as it described by 100m swimming events. Neuromuscular fatigue was estimated by analyzing the physiological changes (high blood lactate concentrations), biomechanical changes in the swimming stroke characteristics (decreased in swimming velocity), and by the changes in the EMG amplitude and frequency parameters at the end of the swimming bout. The amplitude signal of EMG provided by the ARV demonstrated an increase at the end with the respect to the beginning for all muscles under study, excepted for the muscle deltoid anterior. The mean frequency (MNF) in our study decrease at the end of the swimming in the 4th lap relative to the 1st lap for all muscles under observation, along the

  4. Animal models for genetic neuromuscular diseases.

    PubMed

    Vainzof, Mariz; Ayub-Guerrieri, Danielle; Onofre, Paula C G; Martins, Poliana C M; Lopes, Vanessa F; Zilberztajn, Dinorah; Maia, Lucas S; Sell, Karen; Yamamoto, Lydia U

    2008-03-01

    The neuromuscular disorders are a heterogeneous group of genetic diseases, caused by mutations in genes coding sarcolemmal, sarcomeric, and citosolic muscle proteins. Deficiencies or loss of function of these proteins leads to variable degree of progressive loss of motor ability. Several animal models, manifesting phenotypes observed in neuromuscular diseases, have been identified in nature or generated in laboratory. These models generally present physiological alterations observed in human patients and can be used as important tools for genetic, clinic, and histopathological studies. The mdx mouse is the most widely used animal model for Duchenne muscular dystrophy (DMD). Although it is a good genetic and biochemical model, presenting total deficiency of the protein dystrophin in the muscle, this mouse is not useful for clinical trials because of its very mild phenotype. The canine golden retriever MD model represents a more clinically similar model of DMD due to its larger size and significant muscle weakness. Autosomal recessive limb-girdle MD forms models include the SJL/J mice, which develop a spontaneous myopathy resulting from a mutation in the Dysferlin gene, being a model for LGMD2B. For the human sarcoglycanopahties (SG), the BIO14.6 hamster is the spontaneous animal model for delta-SG deficiency, whereas some canine models with deficiency of SG proteins have also been identified. More recently, using the homologous recombination technique in embryonic stem cell, several mouse models have been developed with null mutations in each one of the four SG genes. All sarcoglycan-null animals display a progressive muscular dystrophy of variable severity and share the property of a significant secondary reduction in the expression of the other members of the sarcoglycan subcomplex and other components of the Dystrophin-glycoprotein complex. Mouse models for congenital MD include the dy/dy (dystrophia-muscularis) mouse and the allelic mutant dy(2J)/dy(2J) mouse

  5. Identification of a monoclonal antibody against the leptin receptor that acts as an antagonist and blocks human monocyte and T cell activation.

    PubMed

    Fazeli, Mehdi; Zarkesh-Esfahani, Hamid; Wu, Zida; Maamra, Mabrouka; Bidlingmaier, Martin; Pockley, A Graham; Watson, Philip; Matarese, Giuseppe; Strasburger, Christian J; Ross, Richard J M

    2006-05-30

    Nutritional status has a major impact on the immune response and this is in part mediated by leptin, a pro-inflammatory cytokine. Preliminary data suggest that antagonism of leptin may offer a therapeutic approach for the treatment of some inflammatory disorders. We have tested monoclonal antibodies (mAbs) to the human leptin receptor (ObR) for antagonist activity using a leptin signalling bioassay. We identified a mAb, 9F8, which demonstrated dose-dependent antagonist activity in the leptin bioassay. Specificity of the mAb for ObR was confirmed using a plate binding assay. The 9F8 mAb displaced leptin binding to human ObR and enzymatically generated Fab fragments of 9F8 retained antagonist activity. Therefore the Fab fragment of 9F8 was cloned and recombinant 9F8 Fab (rFab) was purified from E. coli periplasmic fraction using a C-terminal His tag. Purified 9F8 rFab bound to human ObR and exhibited leptin antagonist activity. In vitro studies demonstrated that the 9F8 mAb inhibited leptin induced TNF-alpha production from human monocytes and anti-CD3 mAb induced proliferation of human T cells in PBMC culture. In conclusion, this study has identified a mAb to the human leptin receptor which inhibits leptin signalling and acts as a leptin antagonist in vitro. PMID:16690078

  6. Ionic Blocks

    ERIC Educational Resources Information Center

    Sevcik, Richard S.; Gamble, Rex; Martinez, Elizabet; Schultz, Linda D.; Alexander, Susan V.

    2008-01-01

    "Ionic Blocks" is a teaching tool designed to help middle school students visualize the concepts of ions, ionic compounds, and stoichiometry. It can also assist high school students in reviewing their subject mastery. Three dimensional blocks are used to represent cations and anions, with color indicating charge (positive or negative) and size…

  7. [Neuromuscular biopsy and diagnosis of vasculitis].

    PubMed

    Vital, Anne; Vital, Claude

    2006-09-01

    One characteristic histological lesion on biopsy specimens is mandatory to establish the diagnosis of vasculitis. Combined nerve and muscle biopsies, by the same cutaneous incision, improve significantly the percentage of positive results. Nerve fragments should be taken in every patient presenting sensory manifestations. Such vasculitic lesions are present in medium-sized arterioles and/or small vessels, and correspond mainly to 4 necrotizing vasculitis: panarteritis nodosa (PAN), microscopic polyangiitis (MPA), Churg and Strauss syndrome and Wegener granulomatosis. Microvasculitis should be added to these classical entities, because it corresponds to small vessel wall infiltration by inflammatory cells, as observed in PAN and MPA, but without any necrosis. Microvasculitis has to be differentiated from the inflammatory cell infiltrates surrounding small vessels. However, such perivascular inflammatory cell infiltrates enable the diagnosis of probable vasculitis when associated with clusters of neo-vessels, hemosiderin deposits, or a focal damage of nerve fibers. Grossly, one third of vasculitis diagnosis is confirmed on muscle fragments, a second third on nerve fragments, and the last third on both nerve and muscle fragments. Moreover, in the search for vasculitis, an unpredicted diagnosis of lymphoma or amyloidosis is occasionally established on the neuro-muscular biopsy. PMID:17128151

  8. The gating isomerization of neuromuscular acetylcholine receptors

    PubMed Central

    Auerbach, Anthony

    2010-01-01

    Acetylcholine receptor-channels are allosteric proteins that isomerize (‘gate’) between conformations that have a low vs. high affinity for the transmitter and conductance for ions. In order to comprehend the mechanism by which the affinity and conductance changes are linked it is of value to know the magnitude, timing and distribution of energy flowing through the system. Knowing both the di- and unliganded gating equilibrium constants (E2 and E0) is a foundation for understanding the AChR gating mechanism and for engineering both the ligand and the protein to operate in predictable ways. In adult mouse neuromuscular receptors activated by acetylcholine, E2= 28 and E0≈ 6.5 × 10−7. At each (equivalent) transmitter binding site acetylcholine provides ∼5.2 kcal mol−1 to motivate the isomerization. The partial agonist choline provides ∼3.3 kcal mol−1. The relative time of a residue's gating energy change is revealed by the slope of its rate–equilibrium constant relationship. A map of this parameter suggests that energy propagates as a conformational cascade between the transmitter binding sites and the gate region. Although gating energy changes are widespread throughout the protein, some residues are particularly sensitive to perturbations. Several specific proposals for the structural events that comprise the gating conformational cascade are discussed. PMID:19933754

  9. Neuromuscular dentistry: Occlusal diseases and posture.

    PubMed

    Khan, Mohd Toseef; Verma, Sanjeev Kumar; Maheshwari, Sandhya; Zahid, Syed Naved; Chaudhary, Prabhat K

    2013-01-01

    Neuromuscular dentistry has been a controversial topic in the field of dentistry and still remains debatable. The issue of good occlusion and sound health has been repeatedly discussed. Sometimes we get complains of sensitive teeth and sometimes of tired facial muscles on getting up in the morning. Owing to the intimate relation of masticatory apparatus with the cranium and cervico-scapular muscular system, the disorders in any system, draw attention from concerned clinicians involved in management, to develop an integrated treatment protocol for the suffering patients. There may be patients reporting to the dental clinics after an occlusal restoration or extraction, having pain in or around the temporomandibular joint, headache or neck pain. Although their esthetic demands must not be undermined during the course of treatment plan, whenever dental treatment of any sort is planned, occlusion/bite should be given prime importance. Very few dentist are able to diagnose the occlusal disease and of those who diagnose many people resort to aggressive treatment modalities. This paper aims to report the signs of occlusal disease, and discuss their association with TMDs and posture. PMID:25737904

  10. Stem cell route to neuromuscular therapies.

    PubMed

    Partridge, Terence A

    2003-02-01

    As applied to skeletal muscle, stem cell therapy is a reincarnation of myoblast transfer therapy that has resulted from recent advances in the cell biology of skeletal muscle. Both strategies envisage the reconstruction of damaged muscle from its precursors, but stem cell therapy employs precursors that are earlier in the developmental hierarchy. It is founded on demonstrations of apparently multipotential cells in a wide variety of tissues that can assume, among others, a myogenic phenotype. The main demonstrated advantage of such cells is that they are capable of colonizing many tissues, including skeletal and cardiac muscle via the blood vascular system, thereby providing the potential for a body-wide distribution of myogenic progenitors. From a practical viewpoint, the chief disadvantage is that such colonization has been many orders of magnitude too inefficient to be useful. Proposals for overcoming this drawback are the subject of much speculation but, so far, relatively little experimentation. This review attempts to give some perspective to the status of the stem cell as a therapeutic instrument for neuromuscular disease and to identify issues that need to be addressed for application of this technology. PMID:12548520

  11. Scapholunate Instability: Proprioception and Neuromuscular Control

    PubMed Central

    Salva-Coll, Guillem; Garcia-Elias, Marc; Hagert, Elisabet

    2013-01-01

    From a kinetic point of view, the wrist is considered stable when it is capable of resisting load without suffering injury. Several prerequisites are necessary for the wrist to be kinetically stable: bone morphology, normal articulating surfaces, ligaments, the sensorimotor system, the muscles crossing the wrist, and all nerves connecting to ligaments and muscles. Failure of any one of these factors may result in carpal instability. The terms “scapholunate (SL) dissociation” and “SL instability” refer to one of the most frequent types of wrist instability, resulting from rupture or attenuation of the SL supporting ligaments. From a radiologic point of view, SL instability may be dynamic or static. Unlike static instabilities, which tend to be painful and dysfunctional, a good proportion of dynamic SL instabilities remain asymptomatic and stable for prolonged periods of time. Such a lack of symptoms suggests that a ligament rupture, in itself, is not enough for a joint to become unstable. Certainly, the process of achieving stability is multifactorial and involves normal joint surfaces, ligaments, muscles, and a complex network of neural connections linking all these elements. In this article, we will review the neuromuscular stabilization of the SL joint and the proprioceptive mechanisms that contribute to the dynamic carpal stabilization. PMID:24436806

  12. Vaccination recommendations for patients with neuromuscular disease.

    PubMed

    Esposito, Susanna; Bruno, Claudio; Berardinelli, Angela; Filosto, Massimiliano; Mongini, Tiziana; Morandi, Lucia; Musumeci, Olimpia; Pegoraro, Elena; Siciliano, Gabriele; Tonin, Paola; Marrosu, Gianni; Minetti, Carlo; Servida, Maura; Fiorillo, Chiara; Conforti, Giorgio; Scapolan, Silvia; Ansaldi, Filippo; Vianello, Andrea; Castaldi, Silvana; Principi, Nicola; Toscano, Antonio; Moggio, Maurizio

    2014-10-14

    Neuromuscular diseases (NMDs) encompass a broad spectrum of conditions. Because infections may be relevant to the final prognosis of most NMDs, vaccination appears to be the simplest and most effective solution for protecting NMD patients from vaccine-preventable infections. However, very few studies have evaluated the immunogenicity, safety, tolerability, and efficacy of different vaccines in NMD patients; therefore, detailed vaccination recommendations for NMD patients are not available. Here, we present vaccination recommendations from a group of Italian Scientific Societies for optimal disease prevention in NMD patients that maintain high safety levels. We found that NMD patients can be classified into two groups according to immune function: patients with normal immunity and patients who are immunocompromised, including those who intermittently or continuously take immunosuppressive therapy. Patients with normal immunity and do not take immunosuppressive therapy can be vaccinated as healthy subjects. In contrast, immunocompromised patients, including those who take immunosuppressive therapy, should receive all inactivated vaccines as well as influenza and pneumococcal vaccines; these patients should not be administered live attenuated vaccines. In all cases, the efficacy and long-term persistence of immunity from vaccination in NMD patients can be lower than in normal subjects. Household contacts of immunocompromised NMD patients should also be vaccinated appropriately. PMID:25223270

  13. Musculoskeletal and neuromuscular conditions of instrumental musicians.

    PubMed

    Bejjani, F J; Kaye, G M; Benham, M

    1996-04-01

    Performing Arts Medicine is a broad field that includes the study of medical conditions and injuries incurred by dancers, instrumental musicians, and vocalists. This article summarizes the most relevant literature of approximately the past 10 years concerning the musculoskeletal and neuromuscular conditions of musicians. A literature search was done for relevant articles in English by physicians or scientists. Some older, but fundamental, articles are included; incidental case reports were excluded to the extent possible. Included were articles on incidence, prevalence, pathophysiology, diagnosis, treatment, and biomechanical studies in musicians. Although nearly all of these conditions are the same ones seen in the general work force, it is clear that their occurrence patterns in the professional musician are unique, as is their impact on the life and livelihood of the patient. The content of the Arts Medicine literature does not permit a truly critical review. Research in the last 10 years appears not to have been done in a true blinded, random case-controlled fashion. Many authors support their statements with only their respective clinical experiences. The research cited here includes 58 series, 9 case studies, 5 surveys, 2 pre/post intervention studies, and 1 double-blind crossover clinical trial. PMID:8607768

  14. The neuromuscular differential diagnosis of joint hypermobility.

    PubMed

    Donkervoort, S; Bonnemann, C G; Loeys, B; Jungbluth, H; Voermans, N C

    2015-03-01

    Joint hypermobility is the defining feature of various inherited connective tissue disorders such as Marfan syndrome and various types of Ehlers-Danlos syndrome and these will generally be the first conditions to be considered by geneticists and pediatricians in the differential diagnosis of a patient presenting with such findings. However, several congenital and adult-onset inherited myopathies also present with joint hypermobility in the context of often only mild-to-moderate muscle weakness and should, therefore, be included in the differential diagnosis of joint hypermobility. In fact, on the molecular level disorders within both groups represent different ends of the same spectrum of inherited extracellular matrix (ECM) disorders. In this review we will summarize the measures of joint hypermobility, illustrate molecular mechanisms these groups of disorders have in common, and subsequently discuss the clinical features of: 1) the most common connective tissue disorders with myopathic or other neuromuscular features: Ehlers-Danlos syndrome, Marfan syndrome and Loeys-Dietz syndrome; 2) myopathy and connective tissue overlap disorders (muscle extracellular matrix (ECM) disorders), including collagen VI related dystrophies and FKBP14 related kyphoscoliotic type of Ehlers-Danlos syndrome; and 3) various (congenital) myopathies with prominent joint hypermobility including RYR1- and SEPN1-related myopathy. The aim of this review is to assist clinical geneticists and other clinicians with recognition of these disorders. PMID:25821091

  15. Optimum dose of neostigmine to reverse shallow neuromuscular blockade with rocuronium and cisatracurium.

    PubMed

    Choi, E S; Oh, A Y; Seo, K S; Hwang, J W; Ryu, J H; Koo, B W; Kim, B G

    2016-04-01

    We examined the use of neostigmine for reversing shallow (defined as train-of-four ratio of 0.5), cisatracurium- and rocuronium-induced neuromuscular block in 112 patients, by use of 0 μg.kg(-1) , 10 μg.kg(-1) , 20 μg.kg(-1) or 40 μg.kg(-1) dose of neostigmine for reversal. The times from neostigmine administration to train-of-four ratios of 0.7, 0.9 and 1.0 were evaluated. Analysis of variance showed that the duration of action was significantly longer after cisatracurium compared with rocuronium. The time to reach a train-of-four ratio of 1.0 was significantly shorter with neostigmine 40 μg.kg(-1) compared with lower neostigmine doses, and at this dose the time did not differ between cisatracurium and rocuronium. The recovery time from a train-of-four ratio of 0.5-1.0 did not differ between cisatracurium and rocuronium, and was significantly shortened by the administration of neostigmine. We conclude that a neostigmine dose of 40 μg.kg(-1) was the most effective at reducing recovery time after neuromuscular blockade. PMID:26874258

  16. For the inactivation of mold spores by UVC irradiation, with ozone acting as a promoter, TiO2 nanoparticles may act better as a "sun block" than as a photocatalytic disinfectant.

    PubMed

    Gong, Jia-You; Chen, Yen-Chi; Huang, Yi-Ting; Tsai, Ming-Chien; Yu, Kuo-Pin

    2014-09-01

    Fungal spores are known as critical indoor allergens, and indoor air purification techniques including photocatalytic disinfection using titanium dioxide (TiO2), ultraviolet germicidal irradiation (UVGI) and ozonation, have been considerably investigated. However, most of the research is in regard to photocatalytic disinfection, focused on the anti-bacterial efficacy of TiO2 nanoparticles (NPs). Furthermore, some research even showed that the photocatalytic antifungal efficacy of TiO2 NPs may not be that significant. Thus, investigating the reasons behind the non-significant antifungal efficacy of TiO2 photocatalytic disinfection and enhancing the antifungal efficacy is indispensable. In this study, ozone was employed to improve the photocatalytic antifungal efficacy of the TiO2 NPs and nano-metal supported on TiO2 NPs. The commercial TiO2 NPs (Degussa (Evonik) P25) served as a good support, and incipient wetness impregnation was successfully exploited to prepare oxidized nano-metals (Ag, Cu and Ni) in this study. There were two surfaces (quartz and putty) used in the inactivation experiments of Aspergillus niger spores which were manipulated under two conditions: exposed to ultraviolet (UVC) light , and exposed to UVC and ozone simultaneously. The SEM images demonstrated that the spores were sheltered from UVC light in the microcracks between TiO2 agglomerates. When irradiating with UVC, the A. niger spores on the two testing surfaces, without TiO2 NPs, were inactivated faster than those with TiO2 NPs, implying a "sun block" effect of this material and a lower photocatalytic antifungal efficacy than UVGI. On both surfaces, the inactivation rate constants (k) of A. niger spores exposed to UVC and ozone simultaneously (on quartz: k = 2.09-6.94 h(-1), on putty: k = 3.17-6.66 h(-1)) were better than those exposed to only UVC (on quartz: k = 1.80-5.89 h(-1); on putty: k = 2.97-3.98 h(-1)), indicating ozone can enhance the UVGI antifungal efficacy. PMID:25007943

  17. Using mouse cranial muscles to investigate neuromuscular pathology in vivo.

    PubMed

    Murray, L M; Gillingwater, T H; Parson, S H

    2010-11-01

    Neuromuscular pathology is a classic hallmark of many diseases such as muscular dystrophy, myasthenia gravis, amyotrophic lateral sclerosis and spinal muscular atrophy. It is also a feature of many congenital and acquired myopathies and neuropathies such as diabetic neuropathy and toxin-exposure. The availability of experimentally accessible nerve-muscle preparations from rodent models in which pathological events can be studied in nerve and muscle, as well as at the neuromuscular junction, is therefore of fundamental importance for investigating neuromuscular disease. The group of small cranial muscles, which move the ear in the mouse provide ideal experimental preparations for the study of neuromuscular disease in vivo, but information regarding their anatomical and functional characteristics is currently lacking. Here, we provide a detailed description of the levator auris longus, auricularis superior, abductor auris longus and interscutularis muscles. In addition, we briefly review their differential fibre type and developmental characteristics, which can be exploited to aid our understanding of neuromuscular vulnerability and to provide preferable alternatives to more traditional muscle preparations such as gastrocnemius, soleus and diaphragm. PMID:20637618

  18. Lumbopelvic flexibility modulates neuromuscular responses during trunk flexion-extension.

    PubMed

    Sánchez-Zuriaga, Daniel; Artacho-Pérez, Carla; Biviá-Roig, Gemma

    2016-06-01

    Various stimuli such as the flexibility of lumbopelvic structures influence the neuromuscular responses of the trunk musculature, leading to different load sharing strategies and reflex muscle responses from the afferents of lumbopelvic mechanoreceptors. This link between flexibility and neuromuscular response has been poorly studied. The aim of this study was to investigate the relationship between lumbopelvic flexibility and neuromuscular responses of the erector spinae, hamstring and abdominal muscles during trunk flexion-extension. Lumbopelvic movement patterns were measured in 29 healthy women, who were separated into two groups according to their flexibility during trunk flexion-extension. The electromyographic responses of erector spinae, rectus abdominis and biceps femoris were also recorded. Subjects with greater lumbar flexibility had significantly less pelvic flexibility and vice versa. Subjects with greater pelvic flexibility had a higher rate of relaxation and lower levels of hamstring activation during maximal trunk flexion. The neuromuscular response patterns of the hamstrings seem partially modulated by pelvic flexibility. Not so with the lumbar erector spinae and lumbar flexibility, despite the assertions of some previous studies. The results of this study improve our knowledge of the relationships between trunk joint flexibility and neuromuscular responses, a relationship which may play a role in low back pain. PMID:27155332

  19. Pathophysiological actions of neuropathy-related anti-ganglioside antibodies at the neuromuscular junction

    PubMed Central

    Plomp, Jaap J; Willison, Hugh J

    2009-01-01

    The outer leaflet of neuronal membranes is highly enriched in gangliosides. Therefore, specific neuronal roles have been attributed to this family of sialylated glycosphingolipids, e.g. in modulation of ion channels and transporters, neuronal interaction and recognition, temperature adaptation, Ca2+ homeostasis, axonal growth, (para)node of Ranvier stability and synaptic transmission. Recent developmental, ageing and injury studies on transgenic mice lacking subsets of gangliosides indicate that gangliosides are involved in maintenance rather than development of the nervous system and that ganglioside family members are able to act in a mutually compensatory manner. Besides having physiological functions, gangliosides are the likely antigenic targets of autoantibodies present in Guillain-Barré syndrome (GBS), a group of neuropathies with clinical symptoms of motor- and/or sensory peripheral nerve dysfunction. Antibody binding to peripheral nerves is thought to either interfere with ganglioside function or activate complement, causing axonal damage and thereby disturbed action potential conduction. The presynaptic motor nerve terminal at the neuromuscular junction (NMJ) may be a prominent target because it is highly enriched in gangliosides and lies outside the blood–nerve barrier, allowing antibody access. The ensuing neuromuscular synaptopathy might contribute to the muscle weakness in GBS patients. Several groups, including our own, have studied the effects of anti-ganglioside antibodies in ex vivo and in vivo experimental settings at mouse NMJs. Here, after providing a background overview on ganglioside synthesis, localization and physiology, we will review those studies, which clearly show that anti-ganglioside antibodies are capable of binding to NMJs and thereby can exert a variety of pathophysiological effects. Furthermore, we will discuss the human clinical electrophysiological and histological evidence produced so far of the existence of a neuromuscular

  20. N-glycosylation requirements in neuromuscular synaptogenesis

    PubMed Central

    Parkinson, William; Dear, Mary Lynn; Rushton, Emma; Broadie, Kendal

    2013-01-01

    Neural development requires N-glycosylation regulation of intercellular signaling, but the requirements in synaptogenesis have not been well tested. All complex and hybrid N-glycosylation requires MGAT1 (UDP-GlcNAc:α-3-D-mannoside-β1,2-N-acetylglucosaminyl-transferase I) function, and Mgat1 nulls are the most compromised N-glycosylation condition that survive long enough to permit synaptogenesis studies. At the Drosophila neuromuscular junction (NMJ), Mgat1 mutants display selective loss of lectin-defined carbohydrates in the extracellular synaptomatrix, and an accompanying accumulation of the secreted endogenous Mind the gap (MTG) lectin, a key synaptogenesis regulator. Null Mgat1 mutants exhibit strongly overelaborated synaptic structural development, consistent with inhibitory roles for complex/hybrid N-glycans in morphological synaptogenesis, and strengthened functional synapse differentiation, consistent with synaptogenic MTG functions. Synapse molecular composition is surprisingly selectively altered, with decreases in presynaptic active zone Bruchpilot (BRP) and postsynaptic Glutamate receptor subtype B (GLURIIB), but no detectable change in a wide range of other synaptic components. Synaptogenesis is driven by bidirectional trans-synaptic signals that traverse the glycan-rich synaptomatrix, and Mgat1 mutation disrupts both anterograde and retrograde signals, consistent with MTG regulation of trans-synaptic signaling. Downstream of intercellular signaling, pre- and postsynaptic scaffolds are recruited to drive synaptogenesis, and Mgat1 mutants exhibit loss of both classic Discs large 1 (DLG1) and newly defined Lethal (2) giant larvae [L(2)GL] scaffolds. We conclude that MGAT1-dependent N-glycosylation shapes the synaptomatrix carbohydrate environment and endogenous lectin localization within this domain, to modulate retention of trans-synaptic signaling ligands driving synaptic scaffold recruitment during synaptogenesis. PMID:24227656

  1. Neuromuscular transmission in the athymic nude mouse.

    PubMed

    Schofield, G G; Marshall, I G

    1980-10-01

    No major differences were observed in the mechanical properties of diaphragm, extensor digitorum longus and soleus muscles from athymic nude and control mice. Denervated soleus muscles from nudes and controls showed no significant differences in their sensitivities to the cholinoceptor agonists acetylcholine and carbachol, either in the absence or presence of the anticholinesterase, physostigmine, suggesting that postjunctional receptor function is essentially normal. Phrenic nerve-diaphragm preparations from nudes were less sensitive to the twitch-augmenting effects of neostigmine. No difference in the time course of endplate potentials (epps) between nudes and controls was seen either in the absence or presence of neostigmine. Hence the observed differences in twitch augmentation are unlikely to be due to differences in acetylcholinesterase activity in the two muscles. In normal mice miniature endplate potential (mepp) amplitude decreased and mepp frequency increased with age. These changes were associated with an increase in muscle fibre diameter and a concomitant decrease in membrane resistance. Such changes did not occur in nude mice; thus mepp amplitude remained, high as in young normal muscle. It is suggested that the thymus may play a role in muscle development and that the effects on neuromuscular transmission are secondary to changes in development. In cut diaphragm muscles transmitter reversal potentials in nudes and controls were not different. Although there was no difference in the amplitude of the first epp of a train, or in the immediately releasable acetylcholine store, the quantal content of the first epp, the probability of transmitter release, the total nerve terminal acetylcholine store and the transmitter mobilization rate were all reduced. It is considered probable that all the measurable differences in transmitter release can be explained in terms of the nude muscle fibre diameter being small and being associated with a small nerve terminal

  2. Pain in Youths With Neuromuscular Disease

    PubMed Central

    Engel, Joyce M.; Kartin, Deborah; Carter, Gregory T.; Jensen, Mark P.; Jaffe, Kenneth M.

    2011-01-01

    To examine the prevalence and characteristics of pain in children with neuromuscular disease (NMD), 42 youths with NMD underwent a comprehensive evaluation including a detailed intake interview and structured questionnaire that included demographic and functional data. Youths who reported chronic pain were further queried about pain characteristics, locations, and intensity using an 11-point numerical rating scale and a modified Brief Pain Inventory (BPI). The sample consisted of 24 males (57%) and 18 females (43%), ages ranging from 9 to 20 years (M = 14.8, SD = 2.96). Participants included 14 (37%) with Duchenne-muscular dystrophy, 6 (14%) with myotonic dystrophy, 2 (5%) with Becker dystrophy, 2 (5%) with limb-girdle dystrophy, 2 (5%) with congenital muscular dystrophy, 1 (2%) facioscapulohumeral, and 15 (36%) were classified as “other NMD.” Twenty-one (50%) were ambulatory; 26 (62%) used power wheelchairs/scooters, 9 (2%) used manual wheelchairs, 3 (.07%) used crutches/canes, and 1 (2%) used a walker. A total of 23 (55%) of the youths reported having chronic pain. Current pain intensity was 1.30(range=0–6), mean pain intensity over the past week was 2.39 (range = 0–7), mean pain duration was 8.75 hours (SD=12.84). Pain in the legs was most commonly reported and 83% reported using pain medications. This study indicates that chronic pain is a significant problem in youths with NMD. These data strongly support making comprehensive pain assessment and management an integral part of the standard of care for youths with NMD. PMID:19820205

  3. Single Fiber Electromyographic Jitter to Detect Acute Changes in Neuromuscular Function in Young and Adult Rats

    EPA Science Inventory

    Introduction: Exposure to irreversible cholinesterase (ChE)-inhibiting compounds, such as organophosphates may produce neuromuscular dysfunction. However, less is known about changes in neuromuscular transmission after treatment with reversible ChE-inhibitors. These studies adapt...

  4. Neuromuscular effects of a toxic phospholipase A2 and its nontoxic homologue from the venom of the sea snake, Laticauda colubrina.

    PubMed

    Rowan, E G; Harvey, A L; Takasaki, C; Tamiya, N

    1989-01-01

    A single chain phospholipase A2 (LcPLA-II) and a homologous protein lacking enzymatic activity (LcPLH-I) isolated from the venom of the Solomon Island sea snake (Laticauda colubrina) were tested for effects on neuromuscular transmission and muscle contractility on chick biventer cervicis and mouse hemidiaphragm preparations. LcPLA-II (7.5 nM-1.5 microM) blocked indirectly elicited muscle contractions of both preparations. Low concentrations of LcPLA-II caused little change in sensitivity to acetylcholine, carbachol and KCl. The homologue LcPLH-I (375 nM-1.5 microM) reduced the responses of the biventer cervicis preparation to indirect stimulation and abolished responses to acetylcholine and carbachol, but it did not block KCl responses. These effects were due to minor contamination by a post-junctional neurotoxin. LcPLH-I (375 nM-750 nM) had no effect on indirectly stimulated hemidiaphragm preparations. It is concluded that LcPLA-II blocks neuromuscular transmission by a prejunctional action, and that the homologue lacking phospholipase A2 activity also lacks neuromuscular activity. PMID:2749757

  5. Outcome measures in neuromuscular disease: is the world still flat?

    PubMed

    Lunn, Michael P; Van den Bergh, Peter Y K

    2015-09-01

    Valid, responsive, and meaningful outcome measures for the measurement of the impairment, activity limitations, and quality of life in patients with neuromuscular disease are crucial to identify the natural history of disease and benefits of therapy in clinical practice and trials. Although understanding of many aspects of neuromuscular diseases has advanced dramatically, the development of outcome measures has received less attention. The scales developed from Rasch theory by the PeriNomS Group represent the biggest significant shift in thought in neuromuscular outcome measures for decades. There remain problems with many of them, and further developments are required. However, incorporating them into our outcome sets for daily use and in clinical trials will lead to the more efficient capture of meaningful change and will result in better assessment of individuals and groups of patients in both clinical trials and neurological practice. PMID:26114965

  6. Neuromuscular control and rehabilitation of the unstable ankle

    PubMed Central

    Hung, You-jou

    2015-01-01

    Lateral ankle sprain is a common orthopedic injury with a very high recurrence rate in athletes. After decades of research, it is still unclear what contributes to the high recurrence rate of ankle sprain, and what is the most effective intervention to reduce the incident of initial and recurrent injuries. In addition, clinicians often implement balance training as part of the rehabilitation protocol in hopes of enhancing the neuromuscular control and proprioception of the ankle joint. However, there is no consensus on whether the neuromuscular control and proprioception are compromised in unstable ankles. To reduce the prevalence of ankle sprains, the effectiveness of engaging balance training to enhance the neuromuscular control and proprioception of the ankle joint is also questionable. PMID:26085985

  7. Genetic and evolutionary analysis of the Drosophila larval neuromuscular junction

    NASA Astrophysics Data System (ADS)

    Campbell, Megan

    Although evolution of brains and behaviors is of fundamental biological importance, we lack comprehensive understanding of the general principles governing these processes or the specific mechanisms and molecules through which the evolutionary changes are effected. Because synapses are the basic structural and functional units of nervous systems, one way to address these problems is to dissect the genetic and molecular pathways responsible for morphological evolution of a defined synapse. I have undertaken such an analysis by examining morphology of the larval neuromuscular junction (NMJ) in wild caught D. melanogaster as well as in over 20 other species of Drosophila. Whereas variation in NMJ morphology within a species is limited, I discovered a surprisingly extensive variation among different species. Compared with evolution of other morphological traits, NMJ morphology appears to be evolving very rapidly. Moreover, my data indicate that natural selection rather than genetic drift is primarily responsible for evolution of NMJ morphology. To dissect underlying molecular mechanisms that may govern NMJ growth and evolutionary divergence, I focused on a naturally occurring variant in D. melanogaster that causes NMJ overgrowth. I discovered that the variant mapped to Mob2, a gene encoding a kinase adapter protein originally described in yeast as a member of the Mitotic Exit Network (MEN). I have subsequently examined mutations in the Drosophila orthologs of all the core components of the yeast MEN and found that all of them function as part of a common pathway that acts presynaptically to negatively regulate NMJ growth. As in the regulation of yeast cytokinesis, these components of the MEN appear to act ultimately by regulating actin dynamics during the process of bouton growth and division. These studies have thus led to the discovery of an entirely new role for the MEN---regulation of synaptic growth---that is separate from its function in cell division. This work

  8. Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular Junction

    PubMed Central

    Duregotti, Elisa; Zanetti, Giulia; Scorzeto, Michele; Megighian, Aram; Montecucco, Cesare; Pirazzini, Marco; Rigoni, Michela

    2015-01-01

    Botulinum neurotoxins (BoNTs) and some animal neurotoxins (β-Bungarotoxin, β-Btx, from elapid snakes and α-Latrotoxin, α-Ltx, from black widow spiders) are pre-synaptic neurotoxins that paralyse motor axon terminals with similar clinical outcomes in patients. However, their mechanism of action is different, leading to a largely-different duration of neuromuscular junction (NMJ) blockade. BoNTs induce a long-lasting paralysis without nerve terminal degeneration acting via proteolytic cleavage of SNARE proteins, whereas animal neurotoxins cause an acute and complete degeneration of motor axon terminals, followed by a rapid recovery. In this study, the injection of animal neurotoxins in mice muscles previously paralyzed by BoNT/A or /B accelerates the recovery of neurotransmission, as assessed by electrophysiology and morphological analysis. This result provides a proof of principle that, by causing the complete degeneration, reabsorption, and regeneration of a paralysed nerve terminal, one could favour the recovery of function of a biochemically- or genetically-altered motor axon terminal. These observations might be relevant to dying-back neuropathies, where pathological changes first occur at the neuromuscular junction and then progress proximally toward the cell body. PMID:26670253

  9. Calcitonin gene-related peptide increases acetylcholine quantal size in neuromuscular junctions of mice.

    PubMed

    Gaydukov, Alexander E; Bogacheva, Polina O; Balezina, Olga P

    2016-08-15

    We used an intracellular microelectrode technique to study the mechanisms of action of two isoforms (human and rat) of calcitonin gene-related peptide (CGRP) on the evoked and spontaneous quantal secretion of acetylcholine (ACh) in mouse diaphragm motor synapses. Recordings of miniature endplate potentials (MEPPs) and evoked multiquantal endplate potentials (EPPs) in a cut neuromuscular preparation showed that CGRP increased the amplitude of EPPs without influencing their quantal content. Both isoforms of CGRP in a wide range of concentrations (1nM-1μM) provoked a similar considerable increase in MEPPs amplitude in a dose-dependent manner (up to 150-160% compared to control) without changing their frequency, rise-time, and decay. Inhibition of CGRP-receptors by truncated CGRP (CGRP8-37) completely prevented the potentiating effect of CGRP on the MEPPs amplitude. The effect of CGRP was not accompanied by changes in input resistance of muscle fiber membrane but was fully prevented by inhibition of vesicular ACh transport by vesamicol. Inhibition of protein kinase A (PKA) by H-89 also prevented CGRP action on the MEPPs amplitude. It is concluded that, in mammalian neuromuscular junctions, different isoforms of exogenously applied CGRP uniformly potentiate amplitudes of evoked and spontaneous postsynaptic potentials acting presynaptically via an increase in ACh quantal size. PMID:27288020

  10. Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane

    PubMed Central

    Schmidt, Nadine; Basu, Sreya; Sladecek, Stefan; Gatti, Sabrina; van Haren, Jeffrey; Treves, Susan; Pielage, Jan

    2012-01-01

    Agrin is the major factor mediating the neuronal regulation of postsynaptic structures at the vertebrate neuromuscular junction, but the details of how it orchestrates this unique three-dimensional structure remain unknown. Here, we show that agrin induces the formation of the dense network of microtubules in the subsynaptic cytoplasm and that this, in turn, regulates acetylcholine receptor insertion into the postsynaptic membrane. Agrin acted in part by locally activating phosphatidylinositol 3-kinase and inactivating GSK3β, which led to the local capturing of dynamic microtubules at agrin-induced acetylcholine receptor (AChR) clusters, mediated to a large extent by the microtubule plus-end tracking proteins CLASP2 and CLIP-170. Indeed, in the absence of CLASP2, microtubule plus ends at the subsynaptic muscle membrane, the density of synaptic AChRs, the size of AChR clusters, and the numbers of subsynaptic muscle nuclei with their selective gene expression programs were all reduced. Thus, the cascade linking agrin to CLASP2-mediated microtubule capturing at the synaptic membrane is essential for the maintenance of a normal neuromuscular phenotype. PMID:22851317

  11. Neuromuscular Responses to 14 Weeks of Traditional and Daily Undulating Resistance Training.

    PubMed

    Ullrich, B; Holzinger, S; Soleimani, M; Pelzer, T; Stening, J; Pfeiffer, M

    2015-06-01

    This study compared traditional (TP) and daily undulating (DUP) periodization on muscle strength, EMG-estimated neural drive and muscle architecture of the quadriceps femoris (QF). 10 non-athletic females (24.4±3.2 years) performed 14 weeks of isometric training for the QF exercising 1 leg using TP and the contralateral leg using DUP. Intensities varied from 60% to 80% of MVC and the intensity zones and training volume were equated for each leg. Knee extension MVC, maximal voluntary QF-EMG activity and vastus lateralis (VL) muscle architecture were measured in both legs before, after 6 weeks and after 14 weeks of training using dynamometry, surface EMG and ultrasonography. Isometric MVC and maximal QF-EMG remained unaltered after 6 weeks of training, but were significantly (P<0.05) enhanced after 14 weeks in both legs (MVC: TP 24%, DUP 23%; QF-EMG: TP 45%, DUP 46%). VL-architecture remained unchanged following 6 weeks of training, but VL-muscle thickness (TP 17%, DUP 16%) and fascicle length (TP 16%, DUP 17%) displayed significant (P<0.05) enlargements after 14 weeks in both legs. Importantly, these temporal neuromuscular alterations displayed no significant differences between the training legs. Therefore, periodization may not act as a key trigger for neuromuscular adaptations. PMID:25760153

  12. Dopaminergic modulation of motor neuron activity and neuromuscular function in Drosophila melanogaster.

    PubMed

    Cooper, R L; Neckameyer, W S

    1999-02-01

    Dopamine is found in both neuronal and non-neuronal tissues in the larval stage of the fruit fly, Drosophila melanogaster, and functions as a signaling molecule in the nervous system. Although dopaminergic neurons in the central nervous system (CNS) were previously thought solely to be interneurons, recent studies suggest that dopamine may also act as a neuromodulator in humoral pathways. We examined both application of dopamine on intact larval CNS-segmental preparations and isolated neuromuscular junctions (NMJs). Dopamine rapidly decreased the rhythmicity of the CNS motor activity. Application of dopamine on neuromuscular preparations of the segmental muscles 6 and 7 resulted in a dose-responsive decrease in the excitatory junction potentials (EJPs). With the use of focal, macro-patch synaptic current recordings the quantal evoked transmission showed a depression of vesicular release at concentrations of 10 microM. Higher concentrations (1 mM) produced a rapid decrement in evoked vesicular release. Dopamine did not alter the shape of the spontaneous synaptic currents, suggesting that dopamine does not alter the postsynaptic muscle fiber receptiveness to the glutaminergic motor nerve transmission. The effects are presynaptic in causing a reduction in the number of vesicles that are stimulated to be released due to neural activity. PMID:10327610

  13. Neuromuscular activation patterns during treadmill walking after space flight

    NASA Technical Reports Server (NTRS)

    Layne, C. S.; McDonald, P. V.; Bloomberg, J. J.

    1997-01-01

    Astronauts adopt a variety of neuromuscular control strategies during space flight that are appropriate for locomoting in that unique environment, but are less than optimal upon return to Earth. We report here the first systematic investigation of potential adaptations in neuromuscular activity patterns associated with postflight locomotion. Astronaut-subjects were tasked with walking on a treadmill at 6.4 km/h while fixating a visual target 30 cm away from their eyes after space flights of 8-15 days. Surface electromyography was collected from selected lower limb muscles and normalized with regard to mean amplitude and temporal relation to heel strike. In general, high correlations (more than 0.80) were found between preflight and postflight activation waveforms for each muscle and each subject: however relative activation amplitude around heel strike and toe off was changed as a result of flight. The level of muscle cocontraction and activation variability, and the relationship between the phasic characteristics of the ankle musculature in preparation for toe off also were altered by space flight. Subjects also reported oscillopsia during treadmill walking after flight. These findings indicate that, after space flight, the sensory-motor system can generate neuromuscular-activation strategies that permit treadmill walking, but subtle changes in lower-limb neuromuscular activation are present that may contribute to increased lower limb kinematic variability and oscillopsia also present during postflight walking.

  14. Assessment of Neuromuscular Function Using Percutaneous Electrical Nerve Stimulation.

    PubMed

    Rozand, Vianney; Grosprêtre, Sidney; Stapley, Paul J; Lepers, Romuald

    2015-01-01

    Percutaneous electrical nerve stimulation is a non-invasive method commonly used to evaluate neuromuscular function from brain to muscle (supra-spinal, spinal and peripheral levels). The present protocol describes how this method can be used to stimulate the posterior tibial nerve that activates plantar flexor muscles. Percutaneous electrical nerve stimulation consists of inducing an electrical stimulus to a motor nerve to evoke a muscular response. Direct (M-wave) and/or indirect (H-reflex) electrophysiological responses can be recorded at rest using surface electromyography. Mechanical (twitch torque) responses can be quantified with a force/torque ergometer. M-wave and twitch torque reflect neuromuscular transmission and excitation-contraction coupling, whereas H-reflex provides an index of spinal excitability. EMG activity and mechanical (superimposed twitch) responses can also be recorded during maximal voluntary contractions to evaluate voluntary activation level. Percutaneous nerve stimulation provides an assessment of neuromuscular function in humans, and is highly beneficial especially for studies evaluating neuromuscular plasticity following acute (fatigue) or chronic (training/detraining) exercise. PMID:26436986

  15. Inspiratory muscle training in the patient with neuromuscular disease.

    PubMed

    McCool, F D; Tzelepis, G E

    1995-11-01

    Pulmonary complications due to respiratory muscle dysfunction are commonly a source of morbidity and mortality in patients with neuromuscular diseases. This review discusses the adverse effects of respiratory muscle weakness on pulmonary mechanics and examines the role that inspiratory muscle training may play in reversing pulmonary dysfunction in these individuals. In asymptomatic persons, it is well established that the inspiratory muscles can be trained to increase both force and endurance. In patients with neuromuscular diseases, the effects of training protocols on force and endurance are more controversial. This article reviews seven studies that have evaluated respiratory muscle training in a total of 75 patients with varied neuromuscular disorders. Training regimens included breathing through inspiratory resistive loads and isocapnic hyperpnea. Despite methodologic differences among studies, investigators have generally shown that the inspiratory muscles are similar to other skeletal muscle groups in that they can be trained for both force and endurance in these patients. The training-related improvements in inspiratory muscle performance are more pronounced in patients who are less severely affected by their disease. In those patients who have disease to the extent that they are already retaining carbon dioxide, there is little change in force or endurance with training. In these individuals, the inspiratory muscles may already be working at a level sufficiently severe to provide a training stimulus with each breath. No adverse effects of inspiratory muscle training were reported. Inspiratory muscle training can improve force and endurance in patients with neuromuscular weakness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7480122

  16. Biochemistry of Neuromuscular Diseases: A Course for Undergraduate Students

    ERIC Educational Resources Information Center

    Ohlendieck, Kay

    2002-01-01

    This article outlines an undergraduate course focusing on supramolecular membrane protein complexes involved in the molecular pathogenesis of neuromuscular disorders. The emphasis of this course is to introduce students to the key elements involved in the ion regulation and membrane stabilization during muscle contraction and the role of these…

  17. Neuromuscular Electrical Stimulation for Motor Restoration in Hemiplegia.

    PubMed

    Knutson, Jayme S; Fu, Michael J; Sheffler, Lynne R; Chae, John

    2015-11-01

    This article reviews the most common therapeutic and neuroprosthetic applications of neuromuscular electrical stimulation (NMES) for upper and lower extremity stroke rehabilitation. Fundamental NMES principles and purposes in stroke rehabilitation are explained. NMES modalities used for upper and lower limb rehabilitation are described, and efficacy studies are summarized. The evidence for peripheral and central mechanisms of action is also summarized. PMID:26522909

  18. Drug Development and Challenges for Neuromuscular Clinical Trials.

    PubMed

    El Mouelhi, Mohamed

    2016-03-01

    Drug development process faces many challenges, including those encountered in clinical trials for neuromuscular diseases. Drug development is a lengthy and highly costly process. Out of 10 compounds entering first study in man (phase 1), only one compound reaches the market after an average of 14 years with a cost of $2.7 billion. Nevertheless, according to the Centers for Medicare and Medicaid services, prescription drugs constituted only 9 % of each health care dollar spent in USA in 2013. Examples of challenges encountered in neuromuscular clinical trials include lack of validated patient-reported outcome tools, blinding issues, and the use of placebo in addition to lack of health authority guidance for orphan diseases. Patient enrollment challenge is the leading cause of missed clinical trial deadlines observed in about 80 % of clinical trials, resulting in delayed availability of potentially life-saving therapies. Another specific challenge introduced by recent technology is the use of social media and risk of bias. Sharing personal experiences while in the study could easily introduce bias among patients that would interfere with accurate interpretation of collected data. To minimize this risk, recent neuromuscular studies incorporate as an inclusion criterion the patient's agreement not to share any of study experiences through social media with other patients during the study conduct. Consideration of these challenges will allow timely response to the high unmet medical needs for many neuromuscular diseases. PMID:26691331

  19. Activity-Dependent Regulation of the Binomial Parameters p and n at the Mouse Neuromuscular Junction In Vivo

    PubMed Central

    Wang, Xueyong; Wang, Qingbo; Engisch, Kathrin L.

    2010-01-01

    Block of neurotransmission at the mammalian neuromuscular junction triggers an increase in the number of vesicles released (quantal content). The increase occurs whether nerve and muscle activity are both blocked by placement of a tetrodotoxin (TTX) containing cuff on the nerve or whether muscle activity is selectively blocked by injection of α-bungarotoxin (BTX). We used ANOVA to examine whether the mechanism underlying the increase in quantal content differed between the two types of activity blockade. We found that TTX-induced blockade increased the probability of release (p), whereas BTX-induced blockade increased the number of releasable vesicles (n). The lack of increase in p when postsynaptic activity was blocked with BTX suggests that block of presynaptic activity triggers the increase. To determine whether n is regulated by mismatch of pre- and postsynaptic activity introduced by BTX injection we combined BTX and TTX and still found an increase in n. We conclude that block of acetylcholine binding to acetylcholine receptors during spontaneous release triggers the increase in n. PMID:20739593

  20. Neuromuscular Electrical Stimulation for Mobility Support of Elderly

    PubMed Central

    2015-01-01

    The stimulator for neuromuscular electrical stimulation for mobility support of elderly is not very complicated, but for application within “MOBIL” we have some additional demands to fulfill. First we have specific safety issues for this user group. A powerful compliance management system is crucial not only to guide daily application, but for creating hard data for the scientific outcome. We also need to assure easy handling of the stimulator, because the subjects are generally not able to cope with too difficult and complex motor skills. So, we developed five generations of stimulators and optimizing solutions after field tests. We are already planning the sixth generation with wireless control of the stimulation units by the central main handheld control unit. In a prototype, we have implemented a newly available high capacity memory, a breakthrough in “compliance data storage” as they offer the necessary high storage capacity and fast data handling for an affordable prize. The circuit also contains a 3D accelerometer sensor which acts as a further important safety features: if the control unit drops, this event is detected automatically by the sensor and activates an emergency switch-off that disables the stimulation to avoid associated risks. Further, we have implemented a hardware emergence shutdown and other safety measures. Finally, in the last example muscle torque measurements are referenced with compliance data. In the study normalized maximum voluntary contraction (MVC) and maximum stimulation induced contraction (MSC) were assessed in regular check-ups along the training period. With additional consideration of adjusted stimulation intensity for training out of the compliance data records we are able to estimate the induced contraction strength, which turned out to amount in average 11% of MVC. This value may seem on a first sight rather low, and ought to be considered in relation to the results at the end of the training period. Therefore the

  1. Neuromuscular Electrical Stimulation for Mobility Support of Elderly.

    PubMed

    Mayr, Winfried

    2015-08-24

    The stimulator for neuromuscular electrical stimulation for mobility support of elderly is not very complicated, but for application within "MOBIL" we have some additional demands to fulfill. First we have specific safety issues for this user group. A powerful compliance management system is crucial not only to guide daily application, but for creating hard data for the scientific outcome. We also need to assure easy handling of the stimulator, because the subjects are generally not able to cope with too difficult and complex motor skills. So, we developed five generations of stimulators and optimizing solutions after field tests. We are already planning the sixth generation with wireless control of the stimulation units by the central main handheld control unit. In a prototype, we have implemented a newly available high capacity memory, a breakthrough in "compliance data storage" as they offer the necessary high storage capacity and fast data handling for an affordable prize. The circuit also contains a 3D accelerometer sensor which acts as a further important safety features: if the control unit drops, this event is detected automatically by the sensor and activates an emergency switch-off that disables the stimulation to avoid associated risks. Further, we have implemented a hardware emergence shutdown and other safety measures. Finally, in the last example muscle torque measurements are referenced with compliance data. In the study normalized maximum voluntary contraction (MVC) and maximum stimulation induced contraction (MSC) were assessed in regular check-ups along the training period. With additional consideration of adjusted stimulation intensity for training out of the compliance data records we are able to estimate the induced contraction strength, which turned out to amount in average 11% of MVC. This value may seem on a first sight rather low, and ought to be considered in relation to the results at the end of the training period. Therefore the

  2. Endomicroscopy and electromyography of neuromuscular junctions in situ

    PubMed Central

    Brown, Rosalind; Dissanayake, Kosala N; Skehel, Paul A; Ribchester, Richard R

    2014-01-01

    Objective Electromyography (EMG) is used routinely to diagnose neuromuscular dysfunction in a wide range of peripheral neuropathies, myopathies, and neuromuscular degenerative diseases including motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Definitive neurological diagnosis may also be indicated by the analysis of pathological neuromuscular innervation in motor-point biopsies. Our objective in this study was to preempt motor-point biopsy by combining live imaging with electrophysiological analysis of slow degeneration of neuromuscular junctions (NMJs) in vivo. Methods We combined conventional needle electromyography with fiber-optic confocal endomicroscopy (CEM), using an integrated hand-held, 1.5-mm-diameter probe. We utilized as a test bed, various axotomized muscles in the hind limbs of anaesthetized, double-homozygous thy1.2YFP16: WldS mice, which coexpress the Wallerian-degeneration Slow (WldS) protein and yellow fluorescent protein (YFP) in motor neurons. We also tested exogenous vital stains, including Alexa488-α-bungarotoxin; the styryl pyridinium dye 4-Di-2-Asp; and a GFP conjugate of botulinum toxin Type A heavy chain (GFP-HcBoNT/A). Results We show that an integrated EMG/CEM probe is effective in longitudinal evaluation of functional and morphological changes that take place over a 7-day period during axotomy-induced, slow neuromuscular synaptic degeneration. EMG amplitude declined in parallel with overt degeneration of motor nerve terminals. EMG/CEM was safe and effective when nerve terminals and motor endplates were selectively stained with vital dyes. Interpretation Our findings constitute proof-of-concept, based on live imaging in an animal model, that combining EMG/CEM may be useful as a minimally invasive precursor or alternative to motor-point biopsy in neurological diagnosis and for monitoring local administration of potential therapeutics. PMID:25540801

  3. Effects of regular use of neuromuscular electrical stimulation on tissue health.

    PubMed

    Bogie, Kath M; Triolo, Ronald J

    2003-01-01

    Changes in tissue health were monitored in a group of spinal cord injury (SCI) individuals with the use of an implanted neuromuscular electrical stimulation (NMES) system to provide standing and to facilitate standing transfers. Tissue health was evaluated through monitoring tissue oxygen levels in the ischial region along with measuring interface pressures at the seating support interface. Baseline assessments were done at study enrollment and repeated on completion of a conditioning exercise program. Serial assessments of tissue health were performed on eight NMES implant recipients. Unloaded tissue oxygen levels in the ischial region tended to increase after following the NMES exercise program for 8 weeks. Concurrently, pressure distributions at the seating support interface tended to change such that although the total pressure acting at the interface did not change, ischial region pressures showed a significant decrease. These changes indicate that chronic use of NMES has a quantifiable benefit on tissue health. PMID:15077659

  4. Assessment of neuromuscular dysfunction during poisoning by organophosphorus compounds.

    PubMed

    Thiermann, Horst; Seeger, Thomas; Gonder, Sascha; Herkert, Nadja; Antkowiak, Bernd; Zilker, Thomas; Eyer, Florian; Worek, Franz

    2010-09-01

    Dysfunction of respiratory muscles is a life-threatening complication in poisoning by organophosphorus compounds (OPs). It is both of central and peripheral origin due to impaired cholinergic signalling upon inhibition of acetylcholinesterase (AChE). The dysfunction at neuromuscular synapses is not amenable to anticholinergics and remains a therapeutic challenge. Thus, a clear understanding of the distinct mechanisms occurring at neuromuscular synapses is decisive for the development and improvement of therapeutic strategies, particularly with nerve agent poisoning, where clinical studies are prevented by ethical considerations. Using red blood cell AChE, the kinetics of OP induced inhibition, aging, and spontaneous and oxime-induced reactivation have been elucidated. In a dynamically working in vitro model with real-time determination of membrane-bound AChE, it was shown that the kinetic constants derived from erythrocyte AChE are comparable to muscle AChE in a given species. To assess, whether kinetic considerations of AChE activity are relevant for the neuromuscular function, organotypic spinal cord-skeletal muscle cocultures have been established. In this model neostigmine and VX affected neuromuscular transmission as anticipated from their known actions on AChE. Also oxime-induced restoration of the neuromuscular transmission was observed. These findings were confirmed by functional studies on diaphragm muscles of various species with determination of muscle force generation upon phrenic nerve or indirect electrical field stimulation techniques. Investigations with human intercostal muscles are in progress to assess the conditions in human tissue. The results obtained with paraoxon favourably correlate with data from clinical findings of parathion-poisoned patients where the correlation of neuromuscular transmission with the activity of erythrocyte AChE could be established. In conclusion, a variety of methods are available to follow the microscopic reactions

  5. The Onecut Transcription Factor HNF-6 Regulates in Motor Neurons the Formation of the Neuromuscular Junctions

    PubMed Central

    Audouard, Emilie; Schakman, Olivier; René, Frédérique; Huettl, Rosa-Eva; Huber, Andrea B.; Loeffler, Jean-Philippe; Gailly, Philippe; Clotman, Frédéric

    2012-01-01

    The neuromuscular junctions are the specialized synapses whereby spinal motor neurons control the contraction of skeletal muscles. The formation of the neuromuscular junctions is controlled by a complex interplay of multiple mechanisms coordinately activated in motor nerve terminals and in their target myotubes. However, the transcriptional regulators that control in motor neurons the genetic programs involved in neuromuscular junction development remain unknown. Here, we provide evidence that the Onecut transcription factor HNF-6 regulates in motor neurons the formation of the neuromuscular junctions. Indeed, adult Hnf6 mutant mice exhibit hindlimb muscle weakness and abnormal locomotion. This results from defects of hindlimb neuromuscular junctions characterized by an abnormal morphology and defective localization of the synaptic vesicle protein synaptophysin at the motor nerve terminals. These defects are consequences of altered and delayed formation of the neuromuscular junctions in newborn mutant animals. Furthermore, we show that the expression level of numerous regulators of neuromuscular junction formation, namely agrin, neuregulin-2 and TGF-ß receptor II, is downregulated in the spinal motor neurons of Hnf6 mutant newborn animals. Finally, altered formation of neuromuscular junction-like structures in a co-culture model of wildtype myotubes with mutant embryonic spinal cord slices is rescued by recombinant agrin and neuregulin, indicating that depletion in these factors contributes to defective neuromuscular junction development in the absence of HNF-6. Thus, HNF-6 controls in spinal motor neurons a genetic program that coordinates the formation of hindlimb neuromuscular junctions. PMID:23227180

  6. The ageing neuromuscular system and sarcopenia: a mitochondrial perspective.

    PubMed

    Rygiel, Karolina A; Picard, Martin; Turnbull, Doug M

    2016-08-15

    Skeletal muscles undergo structural and functional decline with ageing, culminating in sarcopenia. The underlying neuromuscular mechanisms have been the subject of intense investigation, revealing mitochondrial abnormalities as potential culprits within both nerve and muscle cells. Implicated mechanisms involve impaired mitochondrial dynamics, reduced organelle biogenesis and quality control via mitophagy, accumulation of mitochondrial DNA (mtDNA) damage and respiratory chain defect, metabolic disturbance, pro-apoptotic signalling, and oxidative stress. This article provides an overview of the cellular mechanisms whereby mitochondria may promote maladaptive changes within motor neurons, the neuromuscular junction (NMJ) and muscle fibres. Lifelong physical activity, which promotes mitochondrial health across tissues, is emerging as an effective countermeasure for sarcopenia. PMID:26921061

  7. [Experimental and pathological changes of the neuromuscular junction].

    PubMed

    Koenig, J; Bauché, S; Ben Ammar, A; Nicolle, D; Rigoard, P; Eymard, B; Hantaï, D

    2009-03-01

    The objective of our study was to investigate the cellular communication between the axon and its postsynaptic targets in the synapse. We used the neuromuscular junction (NMJ) model, which is a highly specialized structure between the nerve, the muscle, and the Schwann cell terminal where the motor neuron orders the muscle to contract. We used experimental models of motor nerve reimplantation in a denervated muscle to determine whether 1) the formation of new NMJ could participate in reinnervation of the muscle necessary to contraction or 2) the blockage of neurotransmitter release using botulinum toxin could be compensated by the formation of new NMJ. We also studied human genetic diseases that affect neuromuscular transmission--congenital myasthenic syndromes--to identify the mutations in the genes coding for synaptic molecules and to analyze the compensatory processes involved in NMJ dysfunction so that muscle contraction can occur in these conditions. PMID:19211115

  8. An overview of neurological and neuromuscular signs in mitochondrial diseases.

    PubMed

    Chaussenot, A; Paquis-Flucklinger, V

    2014-05-01

    Mitochondrial disorders have a broad clinical spectrum and are genetically heterogeneous, involving two genomes. These disorders may be develop at any age, with isolated or multiple system involvement, and any pattern of inheritance. Neurological involvement is the most frequent, and concerns muscular, peripheral and central nervous system. Among these diverse signs, some are suggestive of mitochondrial disease, such as progressive external ophthalmoplegia, exercise intolerance, psychomotor regression, stroke-like episodes, refractory epilepsy and Epilepsia Partialis Continua. Others are less specific and mitochondrial hypothesis may be evocated because of either association of different neuromuscular signs or a multisystemic involvement. This review describes the wealth of this neurological and neuromuscular symptomatology through different syndromes reported in the literature, according to preponderant signs and to modes of inheritance, as key elements to guide genetics testing. PMID:24792434

  9. [Neuromuscular disease: respiratory clinical assessment and follow-up].

    PubMed

    Martínez Carrasco, C; Villa Asensi, J R; Luna Paredes, M C; Osona Rodríguez de Torres, F B; Peña Zarza, J A; Larramona Carrera, H; Costa Colomer, J

    2014-10-01

    Patients with neuromuscular disease are an important group at risk of frequently suffering acute or chronic respiratory failure, which is their main cause of death. They require follow-up by a pediatric respiratory medicine specialist from birth or diagnosis in order to confirm the diagnosis and treat any respiratory complications within a multidisciplinary context. The ventilatory support and the cough assistance have improved the quality of life and long-term survival for many of these patients. In this paper, the authors review the pathophysiology, respiratory function evaluation, sleep disorders, and the most frequent respiratory complications in neuromuscular diseases. The various treatments used, from a respiratory medicine point of view, will be analyzed in a next paper. PMID:24709048

  10. Theory of multichannel magnetic stimulation: toward functional neuromuscular rehabilitation.

    PubMed

    Ruohonen, J; Ravazzani, P; Grandori, F; Ilmoniemi, R J

    1999-06-01

    Human excitable cells can be stimulated noninvasively with externally applied time-varying electromagnetic fields. The stimulation can be achieved either by directly driving current into the tissue (electrical stimulation) or by means of electro-magnetic induction (magnetic stimulation). While the electrical stimulation of the peripheral neuromuscular system has many beneficial applications, peripheral magnetic stimulation has so far only a few. This paper analyzes theoretically the use of multiple magnetic stimulation coils to better control the excitation and also to eventually mimic electrical stimulation. Multiple coils allow electronic spatial adjustment of the shape and location of the stimulus without moving the coils. The new properties may enable unforeseen uses for peripheral magnetic stimulation, e.g., in rehabilitation of patients with neuromuscular impairment. PMID:10356871

  11. Report on Adaptive Force, A Specific Neuromuscular Function

    PubMed Central

    Hoff, Marko; Heinke, Nancy; Bittmann, Frank

    2015-01-01

    In real life motions, as well as in sports, the adaptation of the neuromuscular systems to externally applied forces plays an important role. The term Adaptive Force (AF) shall characterize the ability of the nerve-muscle-system to adapt to impacting external forces during isometric and eccentric muscle action. The focus in this paper is on the concept of this neuromuscular action, which is not yet described in this way. A measuring system was constructed and evaluated for this specific neuromuscular function, but only the main information of the evaluation of the measuring system and the preliminary reference values are mentioned here, while an article with detailed description will be published separately. This paper concentrates on the three following points: 1) What is the peculiarity of this neuromuscular function, introduced as AF? 2) Is the measuring system able to capture its specific characteristics and which phases of measurement occur? 3) It seems reasonable to discuss if AF can be distinguished and classified among the known force concepts. The article describes the measuring system and how it is able to capture special features of real life motions like submaximal intensities and the subjects’ option to react adequately on external varying forces. Furthermore, within one measurement the system records three different force qualities: the isometric submaximal Adaptive Force (AFiso), the maximal isometric Adaptive Force (AFisomax) and the maximal eccentric Adaptive Force (AFeccmax). Each of these phases provide different and unique information on the nerve-muscle-system that are discussed in detail. Important, in terms of the Adaptive Force, seems to be the combination of conditional and coordinative abilities. This project was funded by the Federal Ministry of Economy and Technology (Project ZIM KF2262301FO9). PMID:26913155

  12. An Overview of Cardiac Management in Neuromuscular Disease

    PubMed Central

    Hickey, Renee M.; Cullen, John D.; Sachs, George M.

    2016-01-01

    Muscular dystrophy and myasthenia gravis are two neuromuscular disorders that can involve significant cardiovascular complications. The frequency and severity of cardiac pathology varies widely among the muscular dystrophies. In some, it is nearly inevitable and requires regular evaluation. In others, assessment of cardiac function can be more symptom-driven. On-ly a minority of myasthenic patients manifest disease-related cardiovascular complications; however, their presentation can be rapidly progressive and life-threatening.. PMID:27347224

  13. Report on Adaptive Force, A Specific Neuromuscular Function.

    PubMed

    Hoff, Marko; Schaefer, Laura; Heinke, Nancy; Bittmann, Frank

    2015-09-11

    In real life motions, as well as in sports, the adaptation of the neuromuscular systems to externally applied forces plays an important role. The term Adaptive Force (AF) shall characterize the ability of the nerve-muscle-system to adapt to impacting external forces during isometric and eccentric muscle action. The focus in this paper is on the concept of this neuromuscular action, which is not yet described in this way. A measuring system was constructed and evaluated for this specific neuromuscular function, but only the main information of the evaluation of the measuring system and the preliminary reference values are mentioned here, while an article with detailed description will be published separately. This paper concentrates on the three following points: 1) What is the peculiarity of this neuromuscular function, introduced as AF? 2) Is the measuring system able to capture its specific characteristics and which phases of measurement occur? 3) It seems reasonable to discuss if AF can be distinguished and classified among the known force concepts. The article describes the measuring system and how it is able to capture special features of real life motions like submaximal intensities and the subjects' option to react adequately on external varying forces. Furthermore, within one measurement the system records three different force qualities: the isometric submaximal Adaptive Force (AFiso), the maximal isometric Adaptive Force (AFisomax) and the maximal eccentric Adaptive Force (AFeccmax). Each of these phases provide different and unique information on the nerve-muscle-system that are discussed in detail. Important, in terms of the Adaptive Force, seems to be the combination of conditional and coordinative abilities. This project was funded by the Federal Ministry of Economy and Technology (Project ZIM KF2262301FO9). PMID:26913155

  14. Adiposity is associated with improved neuromuscular reaction time.

    PubMed

    Grantham, James; Henneberg, Maciej

    2014-11-01

    Many studies have focused on the detrimental effects of malnourishment to the performance of the brain and peripheral nerves. Undernourished children and adults have been studied extensively to establish these consequences. Little attention has been given to the body habitus that affects optimum neurological performance and the implications for individuals on the spectral extremes of the healthy weight range. This paper examines the association between markers of adiposity and neurological performance, inclusive of all body types. The data were obtained from Cape Coloured youths (5-20 years) in South Africa from the rural district of Klein Karoo and the urban population of Cape Town. In all, the sums of skin-folds were measured for almost 4000 students. The neuromuscular reaction time was also calculated using a ruler drop test. This measure may serve as a gross marker of peripheral and central neurological performance as both are needed to execute the reflex command. There was a direct correlation between adiposity and neuromuscular reaction time. Whilst controlling for age, increasing fatness was associated with a decrease in neuromuscular reaction time amongst both sexes. This relationship remained statistically significant, even when removing the thinnest 40% of participants, eliminating the scope of influence exerted by malnourishment on the correlation. The trend appears to be more prominent amongst boys. These findings indicate that body lipid reserves are integral to the development of the nervous system even amongst children within the healthy weight ranges. Our hypothesis is that the myelination of the nerves, both centrally through oligodendrocytes and peripherally by Schwann cells, is integral to this process as they are predominantly lipid. Amongst thin but not clinically undernourished individuals, the somatic lipid reserves are modest. These fats may be minimally sequestered away for the development of myelin nerve sheath at the expense of saltatory

  15. Defective Membrane Remodeling in Neuromuscular Diseases: Insights from Animal Models

    PubMed Central

    Muller, Jean; Laporte, Jocelyn

    2012-01-01

    Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1), and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Tooth neuropathies. In addition to centronuclear myopathy, dynamin 2 is also mutated in a dominant form of Charcot-Marie-Tooth neuropathy. While several proteins from these different families are implicated in similar diseases, mutations in close homologues or in the same protein in the case of dynamin 2 lead to diseases affecting different tissues. This suggests (1) a common molecular pathway underlying these different neuromuscular diseases, and (2) tissue-specific regulation of these proteins. This review discusses the pathophysiology of the related neuromuscular diseases on the basis of animal models developed for proteins of the myotubularin, amphiphysin, and dynamin families. A better understanding of the common mechanisms between these neuromuscular disorders will lead to more specific health care and therapeutic approaches. PMID:22496665

  16. Development and plasticity of the Drosophila larval neuromuscular junction

    PubMed Central

    Menon, Kaushiki P.; Carrillo, Robert A.; Zinn, Kai

    2013-01-01

    The Drosophila larval neuromuscular system is relatively simple, containing only 32 motor neurons in each abdominal hemisegment, and its neuromuscular junctions (NMJs) are large, individually specified, and easy to visualize and record from. NMJ synapses exhibit developmental and functional plasticity while displaying stereotyped connectivity. Drosophila Type I NMJ synapses are glutamatergic, while the vertebrate NMJ uses acetylcholine as its primary neurotransmitter. The larval NMJ synapses use ionotropic glutamate receptors (GluRs) that are homologous to AMPA-type glutamate receptors in the mammalian brain, and they have postsynaptic scaffolds that resemble those found in mammalian postsynaptic densities. These features make the Drosophila neuromuscular system an excellent genetic model for the study of excitatory synapses in the mammalian central nervous system. The first section of the review presents an overview of NMJ development. The second section describes genes that regulate NMJ development, including: 1) genes that positively and negatively regulate growth of the NMJ; 2) genes required for maintenance of NMJ bouton structure; 3) genes that modulate neuronal activity and alter NMJ growth; 4) genes involved in trans-synaptic signaling at the NMJ. The third section describes genes that regulate acute plasticity, focusing on translational regulatory mechanisms. Since this review is intended for a developmental biology audience, it does not cover NMJ electrophysiology in detail, and does not review genes for which mutations produce only electrophysiological but no structural phenotypes. PMID:24014452

  17. Methods for Multiloop Identification of Visual and Neuromuscular Pilot Responses.

    PubMed

    Olivari, Mario; Nieuwenhuizen, Frank M; Venrooij, Joost; Bülthoff, Heinrich H; Pollini, Lorenzo

    2015-12-01

    In this paper, identification methods are proposed to estimate the neuromuscular and visual responses of a multiloop pilot model. A conventional and widely used technique for simultaneous identification of the neuromuscular and visual systems makes use of cross-spectral density estimates. This paper shows that this technique requires a specific noninterference hypothesis, often implicitly assumed, that may be difficult to meet during actual experimental designs. A mathematical justification of the necessity of the noninterference hypothesis is given. Furthermore, two methods are proposed that do not have the same limitations. The first method is based on autoregressive models with exogenous inputs, whereas the second one combines cross-spectral estimators with interpolation in the frequency domain. The two identification methods are validated by offline simulations and contrasted to the classic method. The results reveal that the classic method fails when the noninterference hypothesis is not fulfilled; on the contrary, the two proposed techniques give reliable estimates. Finally, the three identification methods are applied to experimental data from a closed-loop control task with pilots. The two proposed techniques give comparable estimates, different from those obtained by the classic method. The differences match those found with the simulations. Thus, the two identification methods provide a good alternative to the classic method and make it possible to simultaneously estimate human's neuromuscular and visual responses in cases where the classic method fails. PMID:25706979

  18. Neuromuscular interactions around the knee in children, adults and elderly

    PubMed Central

    Kellis, Eleftherios; Mademli, Lida; Patikas, Dimitrios; Kofotolis, Nikolaos

    2014-01-01

    Although injury and neuromuscular activation patterns may be common for all individuals, there are certain factors which differentiate neuromuscular activity responses between children, adults and elderly. The purpose of this study is to review recent evidence on age differences in neural activation and muscle balances around the knee when performing single joint movements. Particularly, current evidence indicates that there are some interesting similarities in the neuromuscular mechanisms by which children or the elderly differ compared with adults. Both children and elderly display a lower absolute muscle strength capacity than adults which cannot fully be explained by differences in muscle mass. Quadriceps activation failure is a common symptom of all knee injuries, irrespective of age but it is likely that its effect is more evident in children or adults. While one might expect that antagonist co-activation would differ between age categories, it appears that this is not the case. Although hamstring: quadriceps ratio levels are altered after knee injury, it is not clear whether this is an age specific response. Finally, evidence suggests that both children and the elderly display less stiffness of the quadriceps muscle-tendon unit than adults which affects their knee joint function. PMID:25232523

  19. Neuromuscular properties and functional aspects of taped ankles.

    PubMed

    Lohrer, H; Alt, W; Gollhofer, A

    1999-01-01

    We used electromyographic and goniometric methods to test 40 subjects to describe the neuromuscular and biomechanical adaptation of the ankle with respect to application of two different adhesive tapes and to exercises. The neuromuscular responses to inversion injury simulation, together with the mechanical displacements of the joint complex, were analyzed before and after controlled athletic exercises. The proprioceptive amplification ratio was calculated on the basis of the integrated reflex electromyographic results and on the maximum inversion amplitude. Relevant stability gains were achieved immediately after applying tape. There was reduced tape stability after athletic exercise for one of the two tape materials tested. No further loosening was detected, even after prolonged wearing of tape (24 hours). Compared with the unprotected ankle, the taped ankle had a significant increase in the proprioceptive amplification ratio. Both fatigue and mechanical loosening may be responsible for the significant reduction in this ratio immediately after exercise. After the 24-hour interval, the ratio was increased, which could be explained by physiologic neuromuscular regeneration and mechanical restabilization of the tape itself. The sensitivity of the proprioceptive amplification ratio, both to external stabilization and to internal fatigue, supports its potential value to quantify functional joint stability. PMID:9934422

  20. [Molecular mechanisms underlying the formation of neuromuscular junction].

    PubMed

    Higuchi, Osamu; Yamanashi, Yuji

    2011-07-01

    The neuromuscular junction (NMJ) is a synapse between a motor neuron and skeletal muscle. The contraction of skeletal muscle is controlled by the neurotransmitter acetylcholine (ACh), which is released from the motor nerve terminal. To achieve efficient neuromuscular transmission, acetylcholine receptors (AChRs) must be densely clustered on the muscle membrane of the NMJ. Failure of AChR clustering is associated with disorders of neuromuscular transmission such as congenital myasthenic syndromes (CMS) and myasthenia gravis (MG). Motoneuronal agrin and muscle-specific receptor tyrosine kinase (MuSK) are known to play essential roles in the formation and maintenance of NMJs in the central region of each muscle. However, it had been unclear how agrin activates MuSK. Recent studies have elucidated the roles of several key molecules, including the cytoplasmic adaptor protein Dok-7 and LDL receptor-related protein 4 (Lrp4), in agrin-induced MuSK activation. Moreover, new evidence indicates that cyclin-dependent kinase 5 (Cdk5) regulates postsynaptic differentiation. In this review, we summarize the latest developments in molecular mechanisms underlying NMJ formation in vertebrates. PMID:21747134

  1. A biodynamic feedthrough model based on neuromuscular principles.

    PubMed

    Venrooij, Joost; Abbink, David A; Mulder, Mark; van Paassen, Marinus M; Mulder, Max; van der Helm, Frans C T; Bulthoff, Heinrich H

    2014-07-01

    A biodynamic feedthrough (BDFT) model is proposed that describes how vehicle accelerations feed through the human body, causing involuntary limb motions and so involuntary control inputs. BDFT dynamics strongly depend on limb dynamics, which can vary between persons (between-subject variability), but also within one person over time, e.g., due to the control task performed (within-subject variability). The proposed BDFT model is based on physical neuromuscular principles and is derived from an established admittance model-describing limb dynamics-which was extended to include control device dynamics and account for acceleration effects. The resulting BDFT model serves primarily the purpose of increasing the understanding of the relationship between neuromuscular admittance and biodynamic feedthrough. An added advantage of the proposed model is that its parameters can be estimated using a two-stage approach, making the parameter estimation more robust, as the procedure is largely based on the well documented procedure required for the admittance model. To estimate the parameter values of the BDFT model, data are used from an experiment in which both neuromuscular admittance and biodynamic feedthrough are measured. The quality of the BDFT model is evaluated in the frequency and time domain. Results provide strong evidence that the BDFT model and the proposed method of parameter estimation put forward in this paper allows for accurate BDFT modeling across different subjects (accounting for between-subject variability) and across control tasks (accounting for within-subject variability). PMID:24043420

  2. Neuromuscular conditions for physicians - what you need to know.

    PubMed

    Edwards, Laura; Phillips, Margaret

    2016-06-01

    The Royal College of Physicians (RCP) and the British Society of Rehabilitation Medicine co-hosted a meeting entitled 'Neuromuscular conditions for physicians - what you need to know' at the RCP on 30 November 2015. There was a series of talks, ranging from in-depth genetic and molecular descriptions of pathology to multidisciplinary management of chronic neuromuscular conditions, which stimulated lively debate and discussion. Some overarching themes emerged from the day, most notably: i) the changing expectations and survival rates in Duchenne muscular dystrophy (DMD), which are transforming this disorder into an adult as much as a paediatric condition; ii) the need for integrated management and good communication -between services - whether primary, secondary and tertiary care, medical teams and intensivists, or the multiple teams involved in providing treatment to neuromuscular patients; and iii) in line with the above, the essential need for streamlining care such that patients can avoid spending most of their time attending outpatient appointments, and instead concentrate on living full lives and exploring educational, occupational, leisure and social opportunities. PMID:27251916

  3. Role of Radiologic Imaging in Genetic and Acquired Neuromuscular Disorders

    PubMed Central

    Zanato, Riccardo; Coran, Alessandro; Beltrame, Valeria; Stramare, Roberto

    2015-01-01

    Great technologic and clinical progress have been made in the last two decades in identifying genetic defects of several neuromuscular diseases, as Spinal Muscular Atrophy, genetic muscular dystrophies and other genetic myopathies. The diagnosis is usually challenging, due to great variability in genetic abnormalities and clinical phenotypes and the poor specificity of complementary analyses, i.e., serum creatine kinase (CK) and electrophysiology. Muscle biopsy represents the gold standard for the diagnosis of genetic neuromuscular diseases, but clinical imaging of muscle tissue is an important diagnostic tool to identify and quantifyies muscle damage. Radiologic imaging is, indeed, increasingly used as a diagnostic tool to describe patterns and the extent of muscle involvement, thanks to modern techniques that enable to definethe definition of degrees of muscle atrophy and changes in connective tissue. They usually grade the severity of the disease process with greater accuracy than clinical scores. Clinical imaging is more than complementary to perform muscle biopsy, especially as ultrasound scans are often mandatory to identify the muscle to be biopsied. We will here detail and provideWe will herein provide detailed examples of the radiologic methods that can be used in genetic and acquired neuromuscular disorders, stressing pros and cons. Key Words: Muscle Imaging, MRI, CT, genetic muscle disorders, myopathies, dystrophies PMID:26913153

  4. Fatty replacement of lower paraspinal muscles: normal and neuromuscular disorders

    SciTech Connect

    Hader, H.; Gadoth, N.; Heifetz, H.

    1983-11-01

    The physiologic replacement of the lower paraspinal muscles by fat was evaluated in 157 patients undergoing computed tomography for reasons unrelated to abnormalities of the locomotor system. Five patients with neuromuscular disorders were similarly evaluated. The changes were graded according to severity at three spinal levels: lower thoracic-upper lumbar, midlumbar, and lumbosacral. The results were analyzed in relation to age and gender. It was found that fatty replacement of paraspinal muscles is a normal age-progressive phenomenon most prominent in females. It progresses down the spine, being most advanced in the lumbosacral region. The severest changes in the five patients with neuromuscular disorders (three with poliomyelitis and two with progressive muscular dystrophy) consisted of complete muscle group replacement by fat. In postpoliomyelitis atrophy, the distribution was typically asymmetric and sometimes lacked clinical correlation. In muscular dystrophy, fatty replacement was symmetric, showing relative sparing of the psoas and multifidus muscles. In patients with neuromuscular diseases, computed tomography of muscles may be helpful in planning a better rehabilitation regimen.

  5. Guidelines for ethical behavior relating to clinical practice issues in neuromuscular and electrodiagnostic medicine.

    PubMed

    Abel, Naomi A; De Sousa, Eduardo A; Govindarajan, Raghav; Mayer, Matthew P; Simpson, David A

    2015-12-01

    The American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) developed guidelines to formalize the ethical standards that neuromuscular and electrodiagnostic (EDx) physicians should observe in their clinical and scientific activities. Neuromuscular and EDx medicine is a subspecialty of medicine that focuses on evaluation, diagnosis, and comprehensive medical management, including rehabilitation of individuals with neuromuscular disorders. Physicians working in this subspecialty focus on disorders of the motor unit, including muscle, neuromuscular junction, axon, plexus, nerve root, anterior horn cell, and the peripheral nerves (motor and sensory). The neuromuscular and EDx physician's goal is to diagnose and treat these conditions to mitigate their impact and improve the patient's quality of life. The guidelines are consistent with the Principles of Medical Ethics adopted by the American Medical Association and represent a revision of previous AANEM guidelines. PMID:26372720

  6. Neuromuscular electrical stimulation leads to physiological gains enhancing postural balance in the pre-frail elderly

    PubMed Central

    Mignardot, Jean-Baptiste; Deschamps, Thibault; Le Goff, Camille G; Roumier, François-Xavier; Duclay, Julien; Martin, Alain; Sixt, Marc; Pousson, Michel; Cornu, Christophe

    2015-01-01

    Physiological aging leads to a progressive weakening of muscles and tendons, thereby disturbing the ability to control postural balance and consequently increasing exposure to the risks of falls. Here, we introduce a simple and easy-to-use neuromuscular electrical stimulation (NMES) training paradigm designed to alleviate the postural control deficit in the elderly, the first hallmarks of which present as functional impairment. Nine pre-frail older women living in a long-term care facility performed 4 weeks of NMES training on their plantarflexor muscles, and seven nontrained, non-frail older women living at home participated in this study as controls. Participants were asked to perform maximal voluntary contractions (MVC) during isometric plantarflexion in a lying position. Musculo-tendinous (MT) stiffness was assessed before and after the NMES training by measuring the displacement of the MT junction and related tendon force during MVC. In a standing position, the limit of stability (LoS) performance was determined through the maximal forward displacement of the center of foot pressure, and related postural sway parameters were computed around the LoS time gap, a high force requiring task. The NMES training induced an increase in MVC, MT stiffness, and LoS. It significantly changed the dynamics of postural balance as a function of the tendon property changes. The study outcomes, together with a multivariate analysis of investigated variables, highlighted the benefits of NMES as a potential tool in combating neuromuscular weakening in the elderly. The presented training-based strategy is valuable in alleviating some of the adverse functional consequences of aging by directly acting on intrinsic biomechanical and muscular properties whose improvements are immediately transferable into a functional context. PMID:26229006

  7. Ethical considerations in the management of individuals with severe neuromuscular disorders.

    PubMed

    Bach, J R; Barnett, V

    1994-04-01

    There have been many recent advances in improving the quality of life and prolonging life for individuals with advanced neuromuscular disease. These include the use of physical medicine techniques to balance extremity muscle strength and improve range of motion and noninvasive techniques to provide inspiratory and expiratory muscle assistance to prolong life without resort to tracheostomy. Such advances help eliminate the "crisis" decision making about "going on a respirator" and sophisticated assistive equipment and robotic aids. Physicians and society in general use quality of life issues inappropriately derived by questioning physically able individuals to justify withholding or implementing life-sustaining therapeutic interventions for these individuals. Informed decisions about ethically and financially complex matters such as long-term ventilator use should be made by examining the life satisfaction of competent individuals who have already chosen these options. The great majority of severely disabled ventilator-assisted individuals with neuromuscular disease are satisfied with their lives despite the inability to achieve many of the "usual" goals associated with quality of life in the physically able population. Their principle life satisfaction derives from social relationships, the reorganization of goals and from their immediate environment. Although the Americans with Disabilities Act is seen as an important step to prevent discrimination against disabled individuals, it does little or nothing for the self-directed disabled individual who is not informed by his/her physicians regarding potentially vital therapeutic options nor does it help those who are warehoused in institutions because of lack of a national personal assistance services policy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8148105

  8. Reduced expression of the vesicular acetylcholine transporter and neurotransmitter content affects synaptic vesicle distribution and shape in mouse neuromuscular junction.

    PubMed

    Rodrigues, Hermann A; Fonseca, Matheus de C; Camargo, Wallace L; Lima, Patrícia M A; Martinelli, Patrícia M; Naves, Lígia A; Prado, Vânia F; Prado, Marco A M; Guatimosim, Cristina

    2013-01-01

    In vertebrates, nerve muscle communication is mediated by the release of the neurotransmitter acetylcholine packed inside synaptic vesicles by a specific vesicular acetylcholine transporter (VAChT). Here we used a mouse model (VAChT KD(HOM)) with 70% reduction in the expression of VAChT to investigate the morphological and functional consequences of a decreased acetylcholine uptake and release in neuromuscular synapses. Upon hypertonic stimulation, VAChT KD(HOM) mice presented a reduction in the amplitude and frequency of miniature endplate potentials, FM 1-43 staining intensity, total number of synaptic vesicles and altered distribution of vesicles within the synaptic terminal. In contrast, under electrical stimulation or no stimulation, VAChT KD(HOM) neuromuscular junctions did not differ from WT on total number of vesicles but showed altered distribution. Additionally, motor nerve terminals in VAChT KD(HOM) exhibited small and flattened synaptic vesicles similar to that observed in WT mice treated with vesamicol that blocks acetylcholine uptake. Based on these results, we propose that decreased VAChT levels affect synaptic vesicle biogenesis and distribution whereas a lower ACh content affects vesicles shape. PMID:24260111

  9. Testosterone regulates androgen receptor immunoreactivity in the copulatory, but not courtship, neuromuscular system in adult male green anoles.

    PubMed

    Holmes, M M; Wade, J

    2005-09-01

    Androgens regulate the expression of male reproductive behaviour in diverse vertebrate species, often acting on androgen receptors (AR) to induce structural or functional changes in the nervous system and periphery. Male green anoles possess two sexually dimorphic neuromuscular systems, one controlling throat fan (dewlap) extension, which occurs during courtship, and the other mediating copulatory organ function. Although androgens are required for behavioural activation in both systems, testosterone has differential effects on the neuromuscular morphology. It increases the size of copulatory muscle fibres during the breeding season, but significant effects on dewlap muscle fibre size and motoneurone soma size in either system have not been detected. Corresponding to the lack of testosterone-induced morphological effects in the courtship system, relatively low levels of AR are expressed in the associated motoneurones. The present experiment had two goals, aiming to determine whether: (i) the other courtship and copulatory neuromuscular tissues express AR and (ii) testosterone and/or seasonal environmental changes regulate AR expression. The percentage of AR+ nuclei was evaluated in both the breeding and nonbreeding seasons in gonadally intact adult males (Experiment 1) and in castrated males treated with either testosterone or vehicle (Experiment 2). AR was extensively expressed in the dewlap and copulatory muscles, and in a high percentage of the copulatory motoneurones, but immunoreactivity did not vary across season. Testosterone increased the percentage of AR+ nuclei in the copulatory muscles of both breeding and nonbreeding males but not in the dewlap muscle or copulatory motoneurones. Finally, the target structures for both systems (cartilages and hemipenes) expressed AR in all animals. Therefore, the effects of testosterone on AR immunoreactivity suggest that up-regulation of the receptors may be important for morphological change. However, because all

  10. Block Grants: Federal Data Collection Provisions.

    ERIC Educational Resources Information Center

    General Accounting Office, Washington, DC. Div. of Human Resources.

    This fact sheet compares statutory data collection and reporting provisions of the federal education block grant (chapter 2 of the Education Consolidation and Improvement Act of 1981) with the nine other block grant programs funded in fiscal year 1986; data on statutory administrative cost limits are also provided. Each grant's legislation was…

  11. Use of Single Fiber Electromyographic Jitter to Detect Acute Changes in Neuromuscular Function in Young and Adult Rats

    EPA Science Inventory

    INTRODUCTION: Exposure to irreversible cholinesterase (ChE)-inhibiting compounds, such as organophosphates may produce neuromuscular dysfunction. However, less is known about changes in neuromuscular transmission after treatment with reversible ChE-inhibitors. These studies adapt...

  12. Effects of vesicular acetylcholine uptake blockers on frequency augmentation-potentiation in frog neuromuscular transmission.

    PubMed

    Maeno, T; Enomoto, K

    1994-03-01

    Vesamicol inhibits the vesicular loading of acetylcholine molecules. The effects of vesamicol and similarly acting compounds on neuromuscular transmission in frogs were investigated to determine whether these inhibitors-inhibit the frequency augmentation-potentiation of transmitter release. Various vesicular acetylcholine transport blockers suppressed the stimulation frequency-related release parameter, k, in a dose-dependent manner. Artane, cetiedil, chloroquine, ethodin, quinacrine, vesamicol and its benzyl-analogue, 2-(4-benzylpiperidino)cyclohexanol, had strong effects, while those of aminacrine, chlorpromazine, fluphenazine, imipramine, pyrilamine and thioridazine were weak. A significant correlation was observed between the biochemically reported values of IC50 and the electrophysiological inhibitory potencies on k at 20 microM. Contrary to expectations from the biochemical data, however, vesamicol and its benzyl-analogue showed equipotent inhibitory actions on the electrophysiological frequency augmentation-potentiation relation. Low sensitivity and low selectivity of the frequency augmentation-potentiation for vesamicol and its benzyl-analogue lead us to conclude that the vesicular acetylcholine transporter is not the site of the electrophysiological action of vesamicol and similarly acting chemicals. PMID:8008203

  13. Depression of synaptic efficacy at intermolt in crayfish neuromuscular junctions by 20-hydroxyecdysone, a molting hormone.

    PubMed

    Cooper, R L; Ruffner, M E

    1998-04-01

    This report demonstrates that ecdysteroids can reduce synaptic transmission at an intermolt stage of a crustacean tonic neuromuscular junction by acting at a presynaptic site. The steroid molting hormone, 20-hydroxyecdysone (20-HE), appears to act through a rapid, nongenomic mechanism that decreases the probability of synaptic vesicle release and reduces the number of release sites. Quantal analysis revealed that fewer vesicles were released for a given stimulus when 20-HE was present, and this in turn accounted for the reduced synaptic efficacy. Reduced synaptic efficacy produced smaller evoked postsynaptic currents and smaller excitatory postsynaptic potentials (EPSPs) across the muscle fiber membrane. The reduction in EPSPs was observed among muscle fibers that were innervated by high- or low-output terminals. The behavior of crustaceans/crayfish during the molt cycle, when 20-HE is high, may be explained by the reduction in synaptic transmission. Crustaceans become quiescent during the premolt periods as do insects. The effects of 20-HE can be reversed with the application of the crustacean neuromodulator serotonin, which enhances synaptic transmission. PMID:9535959

  14. Riluzole blocks human muscle acetylcholine receptors

    PubMed Central

    Deflorio, Cristina; Palma, Eleonora; Conti, Luca; Roseti, Cristina; Manteca, Alessia; Giacomelli, Elena; Catalano, Myriam; Limatola, Cristina; Inghilleri, Maurizio; Grassi, Francesca

    2012-01-01

    Riluzole, the only drug available against amyotrophic lateral sclerosis (ALS), has recently been shown to block muscle ACh receptors (AChRs), raising concerns about possible negative side-effects on neuromuscular transmission in treated patients. In this work we studied riluzole's impact on the function of muscle AChRs in vitro and on neuromuscular transmission in ALS patients, using electrophysiological techniques. Human recombinant AChRs composed of α1β1δ subunits plus the γ or ɛ subunit (γ- or ɛ-AChR) were expressed in HEK cells or Xenopus oocytes. In both preparations, riluzole at 0.5 μm, a clinically relevant concentration, reversibly reduced the amplitude and accelerated the decay of ACh-evoked current if applied before coapplication with ACh. The action on γ-AChRs was more potent and faster than on ɛ-AChRs. In HEK outside-out patches, riluzole-induced block of macroscopic ACh-evoked current gradually developed during the initial milliseconds of ACh presence. Single channel recordings in HEK cells and in human myotubes from ALS patients showed that riluzole prolongs channel closed time, but has no effect on channel conductance and open duration. Finally, compound muscle action potentials (CMAPs) evoked by nerve stimulation in ALS patients remained unaltered after a 1 week suspension of riluzole treatment. These data indicate that riluzole, while apparently safe with regard to synaptic transmission, may affect the function of AChRs expressed in denervated muscle fibres of ALS patients, with biological consequences that remain to be investigated. PMID:22431338

  15. Neuromuscular Responses to Simulated Brazilian Jiu-Jitsu Fights

    PubMed Central

    da Silva, Bruno Victor Corrêa; Ide, Bernardo Neme; de Moura Simim, Mário Antônio; Marocolo, Moacir; da Mota, Gustavo Ribeiro

    2014-01-01

    The aim of this study was to investigate the neuromuscular performance responses following successive Brazilian Jiu-Jitsu (BJJ) fights. Twenty-three BJJ athletes (age: 26.3 ± 6.3 years; body mass: 79.4 ± 9.7 kg; body height: 1.80 ± 0.1 m) undertook 3 simulated BJJ fights (10 min duration each separated by 15 min of rest). Neuromuscular performance was measured by the bench press throw (BPT) and vertical counter movement jump (VCMJ) tests, assessed before the 1st fight (Pre) and after the last one (Post). Blood lactate (LA) was measured at Pre, 1 min Post, and 15 min Post fights. Paired t-tests were employed in order to compare the BPT and VCMJ results. One-way ANOVA with Bonferroni post hoc tests were utilized to compare LA responses. The results revealed a significant (p < 0.05) increase in VCMJ performance (40.8 ± 5.5 cm Pre vs. 42.0 ± 5.8 cm Post), but no significant changes in the BPT (814 ± 167 W Pre vs. 835 ± 213 W Post) were observed. LA concentration increased significantly (p < 0.05) at Post, both in the 1st min (10.4 ± 2.7 mmol L-1) and the 15th min (6.4 ± 2.5 mmol L-1) of recovery. We concluded that successive simulated BJJ fights demanded considerable anaerobic contribution of ATP supply, reinforcing the high-intensity intermittent nature of the sport. Nevertheless, no negative impact on acute neuromuscular performance (power) was observed. PMID:25713685

  16. Neuromuscular responses to simulated brazilian jiu-jitsu fights.

    PubMed

    da Silva, Bruno Victor Corrêa; Ide, Bernardo Neme; de Moura Simim, Mário Antônio; Marocolo, Moacir; da Mota, Gustavo Ribeiro

    2014-12-01

    The aim of this study was to investigate the neuromuscular performance responses following successive Brazilian Jiu-Jitsu (BJJ) fights. Twenty-three BJJ athletes (age: 26.3 ± 6.3 years; body mass: 79.4 ± 9.7 kg; body height: 1.80 ± 0.1 m) undertook 3 simulated BJJ fights (10 min duration each separated by 15 min of rest). Neuromuscular performance was measured by the bench press throw (BPT) and vertical counter movement jump (VCMJ) tests, assessed before the 1st fight (Pre) and after the last one (Post). Blood lactate (LA) was measured at Pre, 1 min Post, and 15 min Post fights. Paired t-tests were employed in order to compare the BPT and VCMJ results. One-way ANOVA with Bonferroni post hoc tests were utilized to compare LA responses. The results revealed a significant (p < 0.05) increase in VCMJ performance (40.8 ± 5.5 cm Pre vs. 42.0 ± 5.8 cm Post), but no significant changes in the BPT (814 ± 167 W Pre vs. 835 ± 213 W Post) were observed. LA concentration increased significantly (p < 0.05) at Post, both in the 1st min (10.4 ± 2.7 mmol L-1) and the 15th min (6.4 ± 2.5 mmol L-1) of recovery. We concluded that successive simulated BJJ fights demanded considerable anaerobic contribution of ATP supply, reinforcing the high-intensity intermittent nature of the sport. Nevertheless, no negative impact on acute neuromuscular performance (power) was observed. PMID:25713685

  17. Clinical use of creatine in neuromuscular and neurometabolic disorders.

    PubMed

    Tarnopolsky, Mark A

    2007-01-01

    Many of the neuromuscular (e.g., muscular dystrophy) and neurometabolic (e.g., mitochondrial cytopathies) disorders share similar final common pathways of cellular dysfunction that may be favorably influenced by creatine monohydrate (CrM) supplementation. Studies using the mdx model of Duchenne muscular dystrophy have found evidence of enhanced mitochondrial function, reduced intra-cellular calcium and improved performance with CrM supplementation. Clinical trials in patients with Duchenne and Becker's muscular dystrophy have shown improved function, fat-free mass, and some evidence of improved bone health with CrM supplementation. In contrast, the improvements in function in myotonic dystrophy and inherited neuropathies (e.g., Charcot-Marie-Tooth) have not been significant. Some studies in patients with mitochondrial cytopathies have shown improved muscle endurance and body composition, yet other studies did not find significant improvements in patients with mitochondrial cytopathy. Lower-dose CrM supplementation in patients with McArdle's disease (myophosphorylase deficiency) improved exercise capacity, yet higher doses actually showed some indication of worsened function. Based upon known cellular pathologies, there are potential benefits from CrM supplementation in patients with steroid myopathy, inflammatory myopathy, myoadenylate deaminase deficiency, and fatty acid oxidation defects. Larger randomized control trials (RCT) using homogeneous patient groups and objective and clinically relevant outcome variables are needed to determine whether creatine supplementation will be of therapeutic benefit to patients with neuromuscular or neurometabolic disorders. Given the relatively low prevalence of some of the neuromuscular and neurometabolic disorders, it will be necessary to use surrogate markers of potential clinical efficacy including markers of oxidative stress, cellular energy charge, and gene expression patterns. PMID:18652078

  18. Neuromuscular activity of Bothrops fonsecai snake venom in vertebrate preparations

    PubMed Central

    Fernandes, Carla T; Giaretta, Vânia MA; Prudêncio, Luiz S; Toledo, Edvana O; da Silva, Igor RF; Collaço, Rita CO; Barbosa, Ana M; Hyslop, Stephen; Rodrigues-Simioni, Léa; Cogo, José C

    2014-01-01

    The neuromuscular activity of venom from Bothrops fonsecai, a lancehead endemic to southeastern Brazil, was investigated. Chick biventer cervicis (CBC) and mouse phrenic nerve-diaphragm (PND) preparations were used for myographic recordings and mouse diaphragm muscle was used for membrane resting potential (RP) and miniature end-plate potential (MEPP) recordings. Creatine kinase release and muscle damage were also assessed. In CBC, venom (40, 80 and 160μg/ml) produced concentration- and time-dependent neuromuscular blockade (50% blockade in 85±9 min and 73±8 min with 80 and 160μg/ml, respectively) and attenuated the contractures to 110μM ACh (78–100% inhibition) and 40mM KCl (45–90% inhibition). The venom-induced decrease in twitch-tension in curarized, directly-stimulated preparations was similar to that in indirectly stimulated preparations. Venom (100 and 200μg/ml) also caused blockade in PND preparations (50% blockade in 94±13 min and 49±8 min with 100 and 200μg/ml, respectively) but did not alter the RP or MEPP amplitude. In CBC, venom caused creatine kinase release and myonecrosis. The venom-induced decrease in twitch-tension and in the contractures to ACh and K+ were abolished by preincubating venom with commercial antivenom. These findings indicate that Bothrops fonsecai venom interferes with neuromuscular transmission essentially through postsynaptic muscle damage that affects responses to ACh and KCl. These actions are effectively prevented by commercial antivenom. PMID:25028603

  19. Imaging Acute Neuromuscular Explants from Thy1 Mouse Lines.

    PubMed

    Marinković, Petar; Godinho, Leanne; Misgeld, Thomas

    2015-09-01

    Because core facilities that generate transgenic founder mice for a reasonable fee are now available at most major research institutions, generating new Thy1-XFP transgenic animals (in which XFP stands for any fluorescent protein) is an option even for relatively small laboratories. Here, we provide a protocol for screening offspring of Thy1 transgenic founders. Acute neuromuscular explants are obtained from 3-wk-old F1 mice that have been produced by crossing Thy1 transgenic founders and commercially obtained inbred mice. Thy1-driven expression is detected by fluorescence microscopy. PMID:26330628

  20. To build a synapse: signaling pathways in neuromuscular junction assembly

    PubMed Central

    Wu, Haitao; Xiong, Wen C.; Mei, Lin

    2010-01-01

    Synapses, as fundamental units of the neural circuitry, enable complex behaviors. The neuromuscular junction (NMJ) is a synapse type that forms between motoneurons and skeletal muscle fibers and that exhibits a high degree of subcellular specialization. Aided by genetic techniques and suitable animal models, studies in the past decade have brought significant progress in identifying NMJ components and assembly mechanisms. This review highlights recent advances in the study of NMJ development, focusing on signaling pathways that are activated by diffusible cues, which shed light on synaptogenesis in the brain and contribute to a better understanding of muscular dystrophy. PMID:20215342

  1. Tissue engineering for neuromuscular disorders of the gastrointestinal tract

    PubMed Central

    Koch, Kenneth L; Bitar, Khalil N; Fortunato, John E

    2012-01-01

    The digestive tract is designed for the optimal processing of food that nourishes all organ systems. The esophagus, stomach, small bowel, and colon are sophisticated neuromuscular tubes with specialized sphincters that transport ingested food-stuffs from one region to another. Peristaltic contractions move ingested solids and liquids from the esophagus into the stomach; the stomach mixes the ingested nutrients into chyme and empties chyme from the stomach into the duodenum. The to-and-fro movement of the small bowel maximizes absorption of fat, protein, and carbohydrates. Peristaltic contractions are necessary for colon function and defecation. PMID:23322989

  2. Neuromuscular disease. Diagnosis and discovery in limb-girdle muscular dystrophy.

    PubMed

    Angelini, Corrado

    2016-01-01

    Whole-exome sequencing is a new tool for neuromuscular clinicians, and recent findings show that it improves the diagnosis of limb-girdle muscular dystrophy. The technique has a dual role as a tool for diagnosis and discovery in genetically heterogeneous neuromuscular diseases. PMID:26670295

  3. Neuromuscular determinants of maximum walking speed in well-functioning older adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maximum walking speed may offer an advantage over usual walking speed for clinical assessment of age-related declines in mobility function that are due to neuromuscular impairment. The objective of this study was to determine the extent to which maximum walking speed is affected by neuromuscular fun...

  4. Does quadriceps neuromuscular activation capability explain mobility function among older men and women?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related impairment of neuromuscular activation has been shown to contribute to weakness in older adults. However, it is unclear to what extent impaired neuromuscular activation independently accounts for decline of mobility function. The hypothesis of this study is that capability to produce rap...

  5. Does neuromuscular activation capability explain mobility function among older men and women?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related impairment of neuromuscular activation has been shown to contribute to weakness in older adults. However, it is unclear to what extent impaired neuromuscular activation independently accounts for decline of mobility function. The hypothesis of this study is that capability to produce rap...

  6. Rab3-GEF Controls Active Zone Development at the Drosophila Neuromuscular Junction123

    PubMed Central

    Bae, Haneui; Chen, Shirui; Roche, John P.; Ai, Minrong; Wu, Chunlai

    2016-01-01

    Abstract Synaptic signaling involves the release of neurotransmitter from presynaptic active zones (AZs). Proteins that regulate vesicle exocytosis cluster at AZs, composing the cytomatrix at the active zone (CAZ). At the Drosophila neuromuscular junction (NMJ), the small GTPase Rab3 controls the distribution of CAZ proteins across release sites, thereby regulating the efficacy of individual AZs. Here we identify Rab3-GEF as a second protein that acts in conjunction with Rab3 to control AZ protein composition. At rab3-GEF mutant NMJs, Bruchpilot (Brp) and Ca2+ channels are enriched at a subset of AZs, leaving the remaining sites devoid of key CAZ components in a manner that is indistinguishable from rab3 mutant NMJs. As the Drosophila homologue of mammalian DENN/MADD and Caenorhabditis elegans AEX-3, Rab3-GEF is a guanine nucleotide exchange factor (GEF) for Rab3 that stimulates GDP to GTP exchange. Mechanistic studies reveal that although Rab3 and Rab3-GEF act within the same mechanism to control AZ development, Rab3-GEF is involved in multiple roles. We show that Rab3-GEF is required for transport of Rab3. However, the synaptic phenotype in the rab3-GEF mutant cannot be fully explained by defective transport and loss of GEF activity. A transgenically expressed GTP-locked variant of Rab3 accumulates at the NMJ at wild-type levels and fully rescues the rab3 mutant but is unable to rescue the rab3-GEF mutant. Our results suggest that although Rab3-GEF acts upstream of Rab3 to control Rab3 localization and likely GTP-binding, it also acts downstream to regulate CAZ development, potentially as a Rab3 effector at the synapse. PMID:27022630

  7. Aberrant Subcellular Dynamics of Sigma-1 Receptor Mutants Underlying Neuromuscular Diseases.

    PubMed

    Wong, Adrian Y C; Hristova, Elitza; Ahlskog, Nina; Tasse, Louis-Alexandre; Ngsee, Johnny K; Chudalayandi, Prakash; Bergeron, Richard

    2016-09-01

    The sigma-1 receptor (σ-1R) is an endoplasmic reticulum resident chaperone protein involved in a plethora of cellular functions, and whose disruption has been implicated in a wide range of diseases. Genetic analysis has revealed two σ-1R mutants involved in neuromuscular disorders. A point mutation (E102Q) in the ligand-binding domain results in the juvenile form of amyotrophic lateral sclerosis (ALS16), and a 20 amino-acid deletion (Δ31-50) in the putative cytosolic domain leads to a form of distal hereditary motor neuropathy. We investigated the localization and functional properties of these mutants in cell lines using confocal imaging and electrophysiology. The σ-1R mutants exhibited a significant increase in mobility, aberrant localization, and enhanced block of the inwardly rectifying K(+) channel Kir2.1, compared with the wild-type σ-1R. Thus, these σ-1R mutants have different functional properties that could contribute to their disease phenotypes. PMID:27418673

  8. Resistance to atracurium-induced neuromuscular blockade in patients with intractable seizure disorders treated with anticonvulsants.

    PubMed

    Tempelhoff, R; Modica, P A; Jellish, W S; Spitznagel, E L

    1990-12-01

    Previous studies have demonstrated that, with the exception of atracurium, resistance to the neuromuscular blocking effects of various muscle relaxants develops in patients receiving anticonvulsant therapy. We studied the effects of 0.5 mg/kg IV atracurium in 53 neurosurgical patients: 21 nonepileptic patients receiving no anticonvulsant therapy (MED = 0); 14 epileptic patients treated with carbamazepine for years (MED = 1); and 18 epileptic patients treated with carbamazepine plus either phenytoin or valproic acid for years (MED = 2). The evoked compound electromyogram of the adductor pollicis brevis was recorded, and results were analyzed using analysis of covariance, with weight and age as covariables. The onset time was not significantly different among the three groups. Times for recovery of baseline and train-of-four responses to stimuli were significantly shorter in the MED = 1 and MED = 2 groups than in control patients (MED = 0). The recovery index (time between 25% and 75% recovery of baseline electromyogram values) was progressively shorter in the three groups (MED = 0: 8.02 min; MED = 1: 5.93 min; MED = 2: 1.96 min; P less than 0.001). This study demonstrates that atracurium, when used on epileptic patients requiring long-term (that is, years of) anticonvulsant therapy, has a shorter duration of action than when used in nonepileptic patients. PMID:2240640

  9. Cortical effect and functional recovery by the electromyography-triggered neuromuscular stimulation in chronic stroke patients.

    PubMed

    Shin, Hwa Kyung; Cho, Sang Hyun; Jeon, Hye-seon; Lee, Young-Hee; Song, Jun Chan; Jang, Sung Ho; Lee, Chu-Hee; Kwon, Yong Hyun

    2008-09-19

    We investigated the effect of electromyography (EMG)-triggered neuromuscular electrical stimulation (NMES; EMG-stim) on functional recovery of the hemiparetic hand and the related cortical activation pattern in chronic stroke patients. We enrolled 14 stroke patients, who were randomly assigned to the EMG-stim (n=7) or the control groups (n=7). The EMG-stim was applied to the wrist extensor of the EMG-stim group for two sessions (30 min/session) a day, five times per week for 10 weeks. Four functional tests (box and block, strength, the accuracy index, and the on/offset time of muscle contraction) and functional MRI (fMRI) were performed before and after treatment. fMRI was measured at 1.5 T in parallel with timed finger flexion-extension movements at a fixed rate. Following treatment, the EMG-stim group showed a significant improvement in all functional tests. The main cortical activation change with such functional improvement was shifted from the ipsilateral sensorimotor cortex (SMC) to the contralateral SMC. We demonstrated that 10-week EMG-stim can induce functional recovery and change of cortical activation pattern in the hemiparetic hand of chronic stroke patients. PMID:18644424

  10. Inducible depletion of adult skeletal muscle stem cells impairs the regeneration of neuromuscular junctions.

    PubMed

    Liu, Wenxuan; Wei-LaPierre, Lan; Klose, Alanna; Dirksen, Robert T; Chakkalakal, Joe V

    2015-01-01

    Skeletal muscle maintenance depends on motor innervation at neuromuscular junctions (NMJs). Multiple mechanisms contribute to NMJ repair and maintenance; however muscle stem cells (satellite cells, SCs), are deemed to have little impact on these processes. Therefore, the applicability of SC studies to attenuate muscle loss due to NMJ deterioration as observed in neuromuscular diseases and aging is ambiguous. We employed mice with an inducible Cre, and conditionally expressed DTA to deplete or GFP to track SCs. We found SC depletion exacerbated muscle atrophy and type transitions connected to neuromuscular disruption. Also, elevated fibrosis and further declines in force generation were specific to SC depletion and neuromuscular disruption. Fate analysis revealed SC activity near regenerating NMJs. Moreover, SC depletion aggravated deficits in reinnervation and post-synaptic morphology at regenerating NMJs. Therefore, our results propose a mechanism whereby further NMJ and skeletal muscle decline ensues upon SC depletion and neuromuscular disruption. PMID:26312504

  11. Dopaminergic modulation of neuromuscular transmission in the prawn.

    PubMed Central

    Miller, M W; Parnas, H; Parnas, I

    1985-01-01

    The action of the putative crustacean neurohormone dopamine was examined in the fast extensor musculature of the prawn with intracellular and extracellular recording techniques. Dopamine produced a concentration-dependent (10(-7)-10(-5) M) decrease in the size of the excitatory junctional potential (e.j.p.). It had no effect on the muscle fibre resting membrane potential or input resistance. High concentrations (10(-5)M) of dopamine had no effect on the amplitude distribution or decay time of quantal unit currents, indicating that the agent does not act by blocking post-synaptic receptors or channels. Bath application of dopamine reduced the quantal content at single release sites with a similar time course and concentration dependence as that observed for the e.j.p. Dopamine had no effect on histograms of synaptic delays determined over a 10 degree C range, indicating that it does not modify the time course of phasic neurosecretion. Twin-impulse facilitation experiments showed a marked decrease in the duration of facilitation in the presence of dopamine. These results are interpreted according to recent theoretical and experimental findings as indicating that the dopamine-induced reduction in transmitter release is produced by a decrease in the entry of Ca during the nerve terminal action potential. PMID:2862279

  12. Physiology in Medicine: neuromuscular consequences of diabetic neuropathy.

    PubMed

    Allen, Matti D; Doherty, Timothy J; Rice, Charles L; Kimpinski, Kurt

    2016-07-01

    Diabetic polyneuropathy (DPN) refers to peripheral nerve dysfunction as a complication of diabetes mellitus. This condition is relatively common and is likely a result of vascular and/or metabolic disturbances related to diabetes. In the early or less severe stages of DPN it typically results in sensory impairments but can eventually lead to major dysfunction of the neuromuscular system. Some of these impairments may include muscle atrophy and weakness, slowing of muscle contraction, and loss of power and endurance. Combined with sensory deficits these changes in the motor system can contribute to decreased functional capacity, impaired mobility, altered gait, and increased fall risk. There is no pharmacological disease-modifying therapy available for DPN and the mainstay of treatment is linked to treating the diabetes itself and revolves around strict glycemic control. Exercise therapy (including aerobic, strength, or balance training-based exercise) appears to be a promising preventative and treatment strategy for patients with DPN and those at risk. The goal of this Physiology in Medicine article is to highlight important and overlooked dysfunction of the neuromuscular system as a result of DPN with an emphasis on the physiologic basis for that dysfunction. Additionally, we sought to provide information that clinicians can use when following patients with diabetes or DPN including support for the inclusion of exercise-based therapy as an effective, accessible, and inexpensive form of treatment. PMID:26989220

  13. Age-related changes in the adaptability of neuromuscular output.

    PubMed

    Morrison, Steven; Sosnoff, Jacob J

    2009-05-01

    The aging process is associated with a general decline in biological function. One characteristic that researchers believe represents this diminished functioning of the aging neuromuscular system is increased physiological tremor. The present study is constructed to assess what age-related differences exist in the dynamics of tremor and forearm muscle activity under postural conditions in which the number of arm segments involved in the task was altered. The authors predicted that any alteration in the tremor or electromyographic (EMG) output of these two groups would provide a clearer understanding of the differential effects of aging or task dynamics on physiological function. Results reveal no age-related differences in finger tremor or forearm extensor muscle EMG activity under conditions in which participants were only required to extend their index finger against gravity. However, when participants had to hold their entire upper limb steady against gravity, the authors observed significant increases in forearm EMG activity, finger-tremor amplitude, power in the 8-12-Hz range, and signal regularity between the 2 age groups. The selective changes in signal regularity, EMG activity, and 8-12-Hz tremor amplitude under more challenging postural demands support the view that the age-related changes in neuromuscular dynamics are not fully elucidated when single task demands are utilized. PMID:19366659

  14. Myasthenia and related disorders of the neuromuscular junction.

    PubMed

    Spillane, Jennifer; Beeson, David J; Kullmann, Dimitri M

    2010-08-01

    Our understanding of transmission at the neuromuscular junction has increased greatly in recent years. We now recognise a wide variety of autoimmune and genetic diseases that affect this specialised synapse, causing muscle weakness and fatigue. These disorders greatly affect quality of life and rarely can be fatal. Myasthenia gravis is the most common disorder and is most commonly caused by autoantibodies targeting postsynaptic acetylcholine receptors. Antibodies to muscle-specific kinase (MuSK) are detected in a variable proportion of the remainder. Treatment is symptomatic and immunomodulatory. Lambert-Eaton myasthenic syndrome is caused by antibodies to presynaptic calcium channels, and approximately 50% of cases are paraneoplastic, most often related to small cell carcinoma of the lung. Botulism is an acquired disorder caused by neurotoxins produced by Clostridium botulinum, impairing acetylcholine release into the synaptic cleft. In addition, several rare congenital myasthenic syndromes have been identified, caused by inherited defects in presynaptic, synaptic basal lamina and postsynaptic proteins necessary for neuromuscular transmission. This review focuses on recent advances in the diagnosis and treatment of these disorders. PMID:20547629

  15. Influence of Fatigue in Neuromuscular Control of Spinal Stability

    PubMed Central

    Granata, Kevin P.; Slota, Greg P.; Wilson, Sara E.

    2006-01-01

    Lifting-induced fatigue may influence neuromuscular control of spinal stability. Stability is primarily controlled by muscle recruitment, active muscle stiffness, and reflex response. Fatigue has been observed to affect each of these neuromuscular parameters and may therefore affect spinal stability. A biomechanical model of spinal stability was implemented to evaluate the effects of fatigue on spinal stability. The model included a 6-degree-of-freedom representation of the spine controlled by 12 deformable muscles from which muscle recruitment was determined to simultaneously achieve equilibrium and stability. Fatigue-induced reduction in active muscle stiffness necessitated increased antagonistic cocontraction to maintain stability resulting in increased spinal compression with fatigue. Fatigueinduced reduction in force-generating capacity limited the feasible set of muscle recruitment patterns, thereby restricting the estimated stability of the spine. Electromyographic and trunk kinematics from 21 healthy participants were recorded during sudden-load trials in fatigued and unfatigued states. Empirical data supported the model predictions, demonstrating increased antagonistic cocontraction during fatigued exertions. Results suggest that biomechanical factors including spinal load and stability should be considered when performing ergonomic assessments of fatiguing lifting tasks. Potential applications of this research include a biomechanical tool for the design of administrative ergonomic controls in manual materials handling industries. PMID:15151156

  16. Do palatal lift prostheses stimulate velopharyngeal neuromuscular activity?

    PubMed

    Witt, P D; Rozelle, A A; Marsh, J L; Marty-Grames, L; Muntz, H R; Gay, W D; Pilgram, T K

    1995-11-01

    The purpose of this investigation was to evaluate the ability of palatal lift prostheses to stimulate the neuromuscular activity of the velopharynx. Nasendoscopic evaluations were audio-videotaped preprosthetic and postprosthetic management for 25 patients who underwent placement of a palatal lift prosthesis for velopharyngeal dysfunction (VPD). These audio-videotapes were presented in blinded fashion and random order to three speech pathologists experienced in assessment of patients with VPD. They rated the tapes on the following parameters: VP gap size, closure pattern, orifice estimate, direction and magnitude of change, and qualitative descriptions of the adequacy of VP closure during speech. VP closure for speech was unchanged in 69% of patients and the number of patients rated as improved or deteriorated was nearly identical at about 15%. Postintervention gap shape remained unchanged in 70% of patients. The extent of VP orifice closure during speech remained unchanged in 57% of patients. Articulations that could impair VP function improved in 30% of patients, deteriorating in only 4%. Results of this study neither support the concept that palatal lift prostheses alter the neuromuscular patterning of the velopharynx, nor provide objective documentation of the feasibility of prosthetic reduction for weaning. PMID:8547286

  17. Innervation and neuromuscular control in ageing skeletal muscle.

    PubMed

    Hepple, Russell T; Rice, Charles L

    2016-04-15

    Changes in the neuromuscular system affecting the ageing motor unit manifest structurally as a reduction in motor unit number secondary to motor neuron loss; fibre type grouping due to repeating cycles of denervation-reinnervation; and instability of the neuromuscular junction that may be due to either or both of a gradual perturbation in postsynaptic signalling mechanisms necessary for maintenance of the endplate acetylcholine receptor clusters or a sudden process involving motor neuron death or traumatic injury to the muscle fibre. Functionally, these changes manifest as a reduction in strength and coordination that precedes a loss in muscle mass and contributes to impairments in fatigue. Regular muscle activation in postural muscles or through habitual physical activity can attenuate some of these structural and functional changes up to a point along the ageing continuum. On the other hand, regular muscle activation in advanced age (>75 years) loses its efficacy, and at least in rodents may exacerbate age-related motor neuron death. Transgenic mouse studies aimed at identifying potential mechanisms of motor unit disruptions in ageing muscle are not conclusive due to many different mechanisms converging on similar motor unit alterations, many of which phenocopy ageing muscle. Longitudinal studies of ageing models and humans will help clarify the cause and effect relationships and thus, identify relevant therapeutic targets to better preserve muscle function across the lifespan. PMID:26437581

  18. Intestinal Neuromuscular Function after Preservation and Transplantation1

    PubMed Central

    Hamada, Nobuo; Hutson, William R.; Nakada, Koji; Ikoma, Akira; Suzuki, Tomomi; Zhu, Yue; Starzl, Thomas E.; Todo, Satoru

    2010-01-01

    While it is well known that prolonged preservation of the intestinal graft causes severe mucosal damage after transplantation, little is known about the effect on neuromuscular function. The entire small intestine of adult hound dogs was flushed and preserved with cold lactated Ringer’s solution and autotransplanted either immediately (n = 6) or after 24 hr (n = 6). Animals undergoing sham operation (n = 4) were used as a control. Fasting motility and the response of the intestinal smooth muscle and enteric nerves to bethanechol (100 μg/kg/0.5 hr, iv) and cisapride (0.5 mg/kg, iv) were determined by a multiple strain gauge method on Postoperative Days 2, 4, 7, 14, 21, and 28. Compared to the control, immediately transplanted grafts and those preserved for 24 hr developed delayed reappearance of migrating myoelectric complexes (MMC), hypercontractile activity, and reduced response to bethanechol and cisapride administration. Animals in the preservation group developed more abnormal fasting motility after transplantation, but responses to bethanechol and cisapride stimulation were not markedly different from those of the immediate group. The reappearance of MMC occurred 3 weeks postoperatively in the preservation group compared to 2 days in the immediate group. The results of our study indicate that intestinal dysmotility is augmented in prolonged-preservation grafts compared to those with brief preservation. The dysmotility was transient and normalized 3 to 4 weeks after surgery. Preservation and reperfusion injury to the neuromuscular system of intestinal grafts are reversible and are attenuated by simple hypothermia. PMID:8661243

  19. Predictive Neuromuscular Fatigue of the Lower Extremity Utilizing Computer Modeling.

    PubMed

    Samaan, Michael A; Weinhandl, Joshua T; Hans, Steven A; Bawab, Sebastian Y; Ringleb, Stacie I

    2016-01-01

    This paper studies the modeling of lower extremity muscle forces and their correlation to neuromuscular fatigue. Two analytical fatigue models were combined with a musculoskeletal model to estimate the effects of hamstrings fatigue on lower extremity muscle forces during a side step cut. One of the fatigue models (Tang) used subject-specific knee flexor muscle fatigue and recovery data while the second model (Xia) used previously established fatigue and recovery parameters. Both fatigue models were able to predict hamstrings fatigue within 20% of the experimental data, with the semimembranosus and semitendinosus muscles demonstrating the largest (11%) and smallest (1%) differences, respectively. In addition, various hamstrings fatigue levels (10-90%) on lower extremity muscle force production were assessed using one of the analytical fatigue models. As hamstrings fatigue levels increased, the quadriceps muscle forces decreased by 21% (p < 0.01), while gastrocnemius muscle forces increased by 36% (p < 0.01). The results of this study validate the use of two analytical fatigue models in determining the effects of neuromuscular fatigue during a side step cut, and therefore, this model can be used to assess fatigue effects on risk of lower extremity injury during athletic maneuvers. Understanding the effects of fatigue on muscle force production may provide insight on muscle group compensations that may lead to altered lower extremity motion patterns as seen in noncontact anterior cruciate ligament (ACL) injuries. PMID:26611439

  20. A neuromuscular monitoring system based on a personal computer.

    PubMed

    White, D A; Hull, M

    1992-07-01

    We have developed a computerized neuromuscular monitoring system (NMMS) using commercially available subsystems, i.e., computer equipment, clinical nerve stimulator, force transducer, and strip-chart recorder. This NMMS was developed for acquisition and analysis of data for research and teaching purposes. Computer analysis of the muscle response to stimulation allows graphic and numeric presentation of the twitch response and calculated ratios. Since the system can store and recall data, research data can be accessed for analysis and graphic presentation. An IBM PC/AT computer is used as the central controller and data processor. The computer controls timing of the nerve stimulator output, initiates data acquisition, and adjusts the paper speed of the strip chart recorder. The data processing functions include establishing control response values (when no neuromuscular blockade is present), displaying force versus time and calculated data graphically and numerically, and storing these data for further analysis. The general purpose nature of the computer and strip chart recording equipment allow modification of the system primarily by changes in software. For example, new patterns of nerve stimulation, such as the posttetanic count, can be programmed into the computer system along with appropriate data display and analysis routines. The NMMS has functioned well in the operating room environment. We have had no episodes of electrocautery interference with the computer functions. The automated features have enhanced the utility of the NMMS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1322977

  1. Cystic fibrosis newborn screening: a model for neuromuscular disease screening?

    PubMed

    Scully, Michele A; Farrell, Philip M; Ciafaloni, Emma; Griggs, Robert C; Kwon, Jennifer M

    2015-02-01

    Congenital neuromuscular disorders, such as Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA), and Pompe disease (acid maltase deficiency [AMD]), are candidates for universal newborn screening (NBS). In this article, we discuss the future path of NBS for these disorders with particular emphasis on DMD NBS, because of the likely approval of new gene-modifying treatments, the possible benefits of earlier treatment with corticosteroids, and the recently demonstrated feasibility of a 2-tiered approach to NBS with screening by creatine kinase (CK) levels in dried blood spots followed by mutation detection in those with elevated CK. The cystic fibrosis (CF) NBS program is a successful model for NBS. CF outcomes have consistently improved into adulthood following introduction of CF NBS because considerable resources have been devoted to practices that include: attention to improving laboratory screening, consistent confirmatory testing and immediate referral of all newly diagnosed infants to designated CF care centers that follow established practice guidelines, and ongoing evaluation of CF care centers via a centralized clinical database. Like CF, DMD, SMA, and infantile AMD are inexorably debilitating and require lifetime multidisciplinary clinical management. NBS would address the delays in diagnosis that prevent patients from receiving timely treatments. Standardized care following early diagnosis would reduce disparities in clinical care and outcomes. NBS in these neuromuscular disorders should be implemented, utilizing lessons learned from the past 20 years of CF NBS: standardized protocols for all patients identified by DMD NBS, longitudinal follow-up in multidisciplinary clinics, and coordinated oversight of these clinics. PMID:25425541

  2. Types of Heart Block

    MedlinePlus

    ... Block Explore Heart Block What Is... Electrical System & EKG Results Types Causes Who Is at Risk Signs & ... the P and the R waves on the EKG (electrocardiogram). First-degree heart block may not cause ...

  3. Block ground interaction of rockfalls

    NASA Astrophysics Data System (ADS)

    Volkwein, Axel; Gerber, Werner; Kummer, Peter

    2016-04-01

    During a rockfall the interaction of the falling block with the ground is one of the most important factors that define the evolution of a rockfall trajectory. It steers the rebound, the rotational movement, possibly brake effects, friction losses and damping effects. Therefore, if most reliable rockfall /trajectory simulation software is sought a good understanding of the block ground interaction is necessary. Today's rockfall codes enable the simulation of a fully 3D modelled block within a full 3D surface . However, the details during the contact, i.e. the contact duration, the penetration depth or the dimension of the marks in the ground are usually not part of the simulation. Recent field tests with rocks between 20 and 80 kg have been conducted on a grassy slope in 2014 [1]. A special rockfall sensor [2] within the blocks measured the rotational velocity and the acting accelerations during the tests. External video records and a so-called LocalPositioningSystem deliver information on the travel velocity. With these data not only the flight phases of the trajectories but also the contacts with the ground can be analysed. During the single jumps of a block the flight time, jump length, the velocity, and the rotation are known. During the single impacts their duration and the acting accelerations are visible. Further, the changes of rotational and translational velocity influence the next jump of the block. The change of the rotational velocity over the whole trajectory nicely visualizes the different phases of a rockfall regarding general acceleration and deceleration in respect to the inclination and the topography of the field. References: [1] Volkwein A, Krummenacher B, Gerber W, Lardon J, Gees F, Brügger L, Ott T (2015) Repeated controlled rockfall trajectory testing. [Abstract] Geophys. Res. Abstr. 17: EGU2015-9779. [2] Volkwein A, Klette J (2014) Semi-Automatic Determination of Rockfall Trajectories. Sensors 14: 18187-18210.

  4. 75 FR 65554 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-25

    ... Office of Foreign Assets Control Additional Designations, Foreign Narcotics Kingpin Designation Act... interests in property are blocked pursuant to the Foreign Narcotics Kingpin Designation Act (``Kingpin Act... they are owned or controlled by a specially designated narcotics trafficker. FOR FURTHER...

  5. 75 FR 65554 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-25

    ... Office of Foreign Assets Control Additional Designations, Foreign Narcotics Kingpin Designation Act... interests in property has been blocked pursuant to the Foreign Narcotics Kingpin Designation Act (``Kingpin..., 1999. The Kingpin Act establishes a program targeting the activities of significant foreign...

  6. Mechanisms Regulating Neuromuscular Junction Development and Function and Causes of Muscle Wasting.

    PubMed

    Tintignac, Lionel A; Brenner, Hans-Rudolf; Rüegg, Markus A

    2015-07-01

    The neuromuscular junction is the chemical synapse between motor neurons and skeletal muscle fibers. It is designed to reliably convert the action potential from the presynaptic motor neuron into the contraction of the postsynaptic muscle fiber. Diseases that affect the neuromuscular junction may cause failure of this conversion and result in loss of ambulation and respiration. The loss of motor input also causes muscle wasting as muscle mass is constantly adapted to contractile needs by the balancing of protein synthesis and protein degradation. Finally, neuromuscular activity and muscle mass have a major impact on metabolic properties of the organisms. This review discusses the mechanisms involved in the development and maintenance of the neuromuscular junction, the consequences of and the mechanisms involved in its dysfunction, and its role in maintaining muscle mass during aging. As life expectancy is increasing, loss of muscle mass during aging, called sarcopenia, has emerged as a field of high medical need. Interestingly, aging is also accompanied by structural changes at the neuromuscular junction, suggesting that the mechanisms involved in neuromuscular junction maintenance might be disturbed during aging. In addition, there is now evidence that behavioral paradigms and signaling pathways that are involved in longevity also affect neuromuscular junction stability and sarcopenia. PMID:26109340

  7. Ankle Bracing and the Neuromuscular Factors Influencing Joint Stiffness

    PubMed Central

    Zinder, Steven M; Granata, Kevin P; Shultz, Sandra J; Gansneder, Bruce M

    2009-01-01

    Context: Health care professionals commonly prescribe external stabilization to decrease the incidence and severity of ankle sprains. The mechanism for this decrease is not clearly understood. Examining the effects of ankle bracing on biomechanical stability and influencing factors may provide important information regarding the neuromuscular effects of bracing. Objective: To study the effects of 2 different ankle braces on the neuromuscular factors influencing ankle stiffness. Design: Mixed-model repeated-measures design. Setting: Research laboratory. Patients or Other Participants: Twenty-eight physically active participants composing 2 groups: 14 with unilateral functional ankle instability (age  =  26.19 ± 6.46 years, height  =  166.07 ± 12.90 cm, mass  =  69.90 ± 13.46 kg) and 14 with bilaterally stable ankles (age  =  23.76 ± 5.82 years, height  =  174.00 ± 11.67 cm, mass  =  68.60 ± 13.12 kg). Intervention(s): Participants were fitted with surface electromyography electrodes over the peroneus longus, peroneus brevis, tibialis anterior, and soleus muscles. Each participant received transient motion oscillations to his or her ankle on a custom-built medial-lateral swaying cradle in each of 3 conditions: no ankle brace (NB), lace-up brace (LU), and semirigid brace (SR). Main Outcome Measure(s): Ankle stiffness as measured by the cradle and preactivation levels (percentage of maximal voluntary isometric contraction) of the 4 test muscles. Results: Stiffness levels increased across brace conditions (NB  =  24.79 ± 6.59 Nm/rad, LU  =  28.29 ± 7.05 Nm/rad, SR  =  33.22 ± 8.78 Nm/rad; F2,52  =  66.185, P < .001). No differences were found between groups for rotational stiffness (stable  =  27.36 ± 6.17 Nm/rad, unstable  =  30.18 ± 8.21 Nm/rad; F1,26  =  1.084, P  =  .307). Preactivation levels did not change for any of the tested muscles with the application of an ankle brace (F2,52  =  1.326, P

  8. Neuromuscular action of Bothrops lanceolatus (Fer de lance) venom and a caseinolytic fraction.

    PubMed

    Lôbo de Araújo, Albetiza; Donato, José Luiz; Leite, Gildo Bernardo; Prado-Franceschi, Júlia; Fontana, Marcos Dias; Bon, Cassian; Rodrigues Simioni, Léa

    2002-09-01

    A protein capable of inducing neuromuscular blockade in avian preparations and of depolarizing mouse diaphragm muscle was isolated from Bothrops lanceolatus venom using gel filtration and ion-exchange chromatography. The purified protein was a single chain polypeptide with an estimated molecular mass of 27.5 kDa by SDS-PAGE and had caseinolytic activity (13.3 units/mg), but no phospholipase A(2). B.lanceolatus venom (50 micro g/ml) and the caseinolytic protein (20 micro g/ml) produced contracture and progressive irreversible blockade (50% in 25+/-5 min (SEM) and 45+/-15 min, respectively), in indirectly stimulated chick biventer cervicis preparations. The contractile responses to acetylcholine (ACh; 37 and 74 micro M, n=6) were inhibited by venom and the caseinolytic protein, whereas those to potassium (13.4mM, n=6) were not. Membrane resting potential measurements in mouse hemidiaphragm preparations showed that B.lanceolatus venom and the purified protein caused depolarization which was prevented by D-tubocurarine (14.6mM). The venom produced a slight increase in the amplitude and frequency of miniature end-plate potentials, but this effect was not seen with the purified fraction. These results suggest that the purified protein acts exclusively post-synaptically. PMID:12220713

  9. Distinct Roles of Muscle and Motoneuron LRP4 in Neuromuscular Junction Formation

    PubMed Central

    Wu, Haitao; Lu, Yisheng; Shen, Chengyong; Patel, Neil; Gan, Lin; Xiong, Wen C.; Mei, Lin

    2012-01-01

    SUMMARY Neuromuscular junction (NMJ) formation requires precise interaction between motoneurons and muscle fibers. LRP4 is a receptor of agrin that is thought to act incis to stimulate MuSK in muscle fibers for postsynaptic differentiation. Here we dissected the roles of LRP4 in muscle fibers and motoneurons in NMJ formation by cell-specific mutation. Studies of muscle-specific mutants suggest that LRP4 is involved in deciding where to form AChR clusters in muscle fibers, postsynaptic differentiation, and axon terminal development. LRP4 in HEK293 cells increased synapsin or SV2 puncta in contacting axons of co-cultured neurons, suggesting a synaptogenic function. Analysis of LRP4 muscle and motoneuron double mutants and mechanistic studies suggest that NMJ formation may also be regulated by LRP4 in motoneurons, which could serve as agrin’s receptor in trans to induce AChR clusters. These observations uncovered distinct roles of LRP4 in motoneurons and muscles in NMJ development. PMID:22794264

  10. Distinct roles of muscle and motoneuron LRP4 in neuromuscular junction formation.

    PubMed

    Wu, Haitao; Lu, Yisheng; Shen, Chengyong; Patel, Neil; Gan, Lin; Xiong, Wen C; Mei, Lin

    2012-07-12

    Neuromuscular junction (NMJ) formation requires precise interaction between motoneurons and muscle fibers. LRP4 is a receptor of agrin that is thought to act in cis to stimulate MuSK in muscle fibers for postsynaptic differentiation. Here we dissected the roles of LRP4 in muscle fibers and motoneurons in NMJ formation by cell-specific mutation. Studies of muscle-specific mutants suggest that LRP4 is involved in deciding where to form AChR clusters in muscle fibers, postsynaptic differentiation, and axon terminal development. LRP4 in HEK293 cells increased synapsin or SV2 puncta in contacting axons of cocultured neurons, suggesting a synaptogenic function. Analysis of LRP4 muscle and motoneuron double mutants and mechanistic studies suggest that NMJ formation may also be regulated by LRP4 in motoneurons, which could serve as agrin's receptor in trans to induce AChR clusters. These observations uncovered distinct roles of LRP4 in motoneurons and muscles in NMJ development. PMID:22794264

  11. Nonmechanical Roles of Dystrophin and Associated Proteins in Exercise, Neuromuscular Junctions, and Brains

    PubMed Central

    Nichols, Bailey; Takeda, Shin’ichi; Yokota, Toshifumi

    2015-01-01

    Dystrophin-glycoprotein complex (DGC) is an important structural unit in skeletal muscle that connects the cytoskeleton (f-actin) of a muscle fiber to the extracellular matrix (ECM). Several muscular dystrophies, such as Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophies (dystroglycanopathies), and limb-girdle muscular dystrophies (sarcoglycanopathies), are caused by mutations in the different DGC components. Although many early studies indicated DGC plays a crucial mechanical role in maintaining the structural integrity of skeletal muscle, recent studies identified novel roles of DGC. Beyond a mechanical role, these DGC members play important signaling roles and act as a scaffold for various signaling pathways. For example, neuronal nitric oxide synthase (nNOS), which is localized at the muscle membrane by DGC members (dystrophin and syntrophins), plays an important role in the regulation of the blood flow during exercise. DGC also plays important roles at the neuromuscular junction (NMJ) and in the brain. In this review, we will focus on recently identified roles of DGC particularly in exercise and the brain. PMID:26230713

  12. Physiologically identified 5-HT2-like receptors at the crayfish neuromuscular junction.

    PubMed

    Tabor, Jami N; Cooper, Robin L

    2002-04-01

    The model synaptic preparation of the crayfish opener neuromuscular junction is known to be responsive to exogenous application of 5-HT. The primary effect of 5-HT is an enhancement of vesicular release from the presynaptic motor nerve terminal. 5-HT is known to act through an IP(3) cascade which suggests the presence of a 5-HT(2) receptor subtype; however, this is based on vertebrate 5-HT receptor classification. We examined this possibility by using a selective agonist and two antagonists of the vertebrate 5-HT(2) receptor subtypes. The antagonist ketanserin and spiperone reduce the responsiveness of 5-HT in a dose-dependent manner. The broad 5-HT(2) receptor agonist, alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT) enhances synaptic transmission, in a concentration-dependent manner, but it is not as potent as 5-HT. These results support the notion that a 5-HT(2) receptor subtype is present presynaptically on the crayfish motor nerve terminals. By knowing the types of 5-HT receptors present on the presynaptic motor nerve terminals in this model synaptic preparation, a better understanding of the mechanisms of action of 5-HT on vesicular release will be forthcoming. PMID:11911865

  13. The Role of Musculoskeletal Dynamics and Neuromuscular Control in Stress Development in Bone

    NASA Technical Reports Server (NTRS)

    DeWoody, Yssa

    1996-01-01

    The role of forces produced by the musculotendon units in the stress development of the long bones during gait has not been fully analyzed. It is well known that the musculotendons act as actuators producing the joint torques which drive the body. Although the joint torques required to perform certain motor tasks can be recovered through a kinematic analysis, it remains a difficult problem to determine the actual forces produced by each muscle that resulted in these torques. As a consequence, few studies have focused on the role of individual muscles in the development of stress in the bone. This study takes a control theoretic approach to the problem. A seven-link, eight degrees of freedom model of the body is controlled by various muscle groups on each leg to simulate gait. The simulations incorporate Hill-type models of muscles with activation and contraction dynamics controlled through neural inputs. This direct approach allows one to know the exact muscle forces exerted by each musculotendon throughout the gait cycle as well the joint torques and reaction forces at the ankle and knee. Stress and strain computed by finite element analysis on skeletal members will be related to these derived loading conditions. Thus the role of musculoskeletal dynamics and neuromuscular control in the stress development of the tibia during gait can be analyzed.

  14. Structural Mechanisms of the Agrin-LRP4-MuSK Signaling Pathway in Neuromuscular Junction Differentiation

    PubMed Central

    Zong, Yinong; Jin, Rongsheng

    2015-01-01

    The neuromuscular junction (NMJ) is the most extensively studied model of neuronal synaptogenesis. Acetylcholine receptor (AChR) clustering on the postsynaptic membrane is a cardinal event in the differentiation of NMJs. AChR clustering and postsynaptic differentiation is orchestrated by sophisticated interactions among three proteins: the neuron-secreted proteoglycan agrin, the co-receptor LRP4, and the muscle-specific receptor tyrosine kinase MuSK. LRP4 and MuSK act as scaffolds for multiple binding partners, resulting in a complex and dynamic network of interacting proteins that is required for AChR clustering. In this review, we discuss the structural basis for NMJ postsynaptic differentiation mediated by the agrin-LRP4-MuSK signaling pathway. PMID:23178848

  15. Structural mechanisms of the agrin-LRP4-MuSK signaling pathway in neuromuscular junction differentiation.

    PubMed

    Zong, Yinong; Jin, Rongsheng

    2013-09-01

    The neuromuscular junction (NMJ) is the most extensively studied model of neuronal synaptogenesis. Acetylcholine receptor (AChR) clustering on the postsynaptic membrane is a cardinal event in the differentiation of NMJs. AChR clustering and postsynaptic differentiation is orchestrated by sophisticated interactions among three proteins: the neuron-secreted proteoglycan agrin, the co-receptor LRP4, and the muscle-specific receptor tyrosine kinase MuSK. LRP4 and MuSK act as scaffolds for multiple binding partners, resulting in a complex and dynamic network of interacting proteins that is required for AChR clustering. In this review, we discuss the structural basis for NMJ postsynaptic differentiation mediated by the agrin-LRP4-MuSK signaling pathway. PMID:23178848

  16. Properties of the larval neuromuscular junction in Drosophila melanogaster.

    PubMed Central

    Jan, L Y; Jan, Y N

    1976-01-01

    The anatomy and physiology of the Drosophila larval neuromuscular junction were studied. 2. The dependence of muscle resting potentials on [K+]o and [Na+]o follows the Goldman-Hodgkin-Katz equation (PNa/PK=0-23). Chloride ions distribute passively across the membrane. 3. The mean specific membrane resistance of muscle fibres is 4-3 X 10(3) omega cm2, and the mean specific membrane capacitance is 7-1 muF/cm2. The muscle fibre is virtually isopotential. 4.Transmitter release is quantal. Both the miniature excitatory junctional potential and the evoked release follow the Poisson distribution. 5. Transmitter release depends on approximately the fourth power of [Ca2+]o. If Sr2+ replaces Ca2+, it depends on approximately the fourth power of [Sr2+]o. Mg2+ reduces transmitter release without altering the fourth power dependence on [Ca2+]o. Images A B A B Plate 3 PMID:11339

  17. Diverticular Disease of the Colon: Neuromuscular Function Abnormalities.

    PubMed

    Bassotti, Gabrio; Villanacci, Vincenzo; Bernardini, Nunzia; Dore, Maria P

    2016-10-01

    Colonic diverticular disease is a frequent finding in daily clinical practice. However, its pathophysiological mechanisms are largely unknown. This condition is likely the result of several concomitant factors occurring together to cause anatomic and functional abnormalities, leading as a result to the outpouching of the colonic mucosa. A pivotal role seems to be played by an abnormal colonic neuromuscular function, as shown repeatedly in these patients, and by an altered visceral perception. There is recent evidence that these abnormalities might be related to the derangement of the enteric innervation, to an abnormal distribution of mucosal neuropeptides, and to low-grade mucosal inflammation. The latter might be responsible for the development of visceral hypersensitivity, often causing abdominal pain in a subset of these patients. PMID:27622368

  18. Pitfalls in Using Electrophysiological Studies to Diagnose Neuromuscular Disorders

    PubMed Central

    Koo, Yong Seo; Cho, Charles S.

    2012-01-01

    Electrodiagnostic testing is used widely for the full characterization of neuromuscular disorders and for providing unique information on the processes underlying the pathology of peripheral nerves and muscles. However, such testing should be considered as an extension of anamnesis and physical examination, not as pathognomonic of a specific disease entity. There are many pitfalls that could lead to erroneous interpretation of electrophysiological study results when the studies are not performed properly or if they are performed in the presence of anatomical aberrations. The diagnostic reliability of electrodiagnostic studies can be improved and the associated pitfalls overcome if the physician is familiar with all of those possible pitfalls. In this article we discuss the most common and important pitfalls associated with electrodiagnostic medicine. PMID:22523508

  19. [Effect of berberine, glaucine, stephaglabrine and sanguiritrine on neuromuscular transmission].

    PubMed

    Bitkov, V V; Khashaev, Kh -M; Pronevich, L A; Nenashev, V A; Batrakov, S G

    1991-01-01

    Natural alkaloid drugs, glaucine, stephaglabrine and sanguiritrine, are shown to affect the synaptic transmission in a fairly complicated manner and seem to involve several different mechanisms of action. These substances as well as berberine reduce amplitude of the spontaneous miniature end plate potentials in a frog neuromuscular junction. At low concentrations all the mentioned alkaloids diminish frequency of miniature potentials, but increase it when their concentration exceeds a certain value. Sanguiritrine is the most active in this respect (nearly a 100-fold increase), that is probably associated with its uncoupling effect on the mitochondrial oxidative phosphorylation. Sanguiritrine and stephaglabrine both cause repeated muscle contractions, that is in line with their anti-cholinesterase properties. Glaucine provokes only muscle contracture if present at relatively high concentration. PMID:1652103

  20. Bone Health and Associated Metabolic Complications in Neuromuscular Diseases

    PubMed Central

    Joyce, Nanette C.; Hache, Lauren P.; Clemens, Paula R.

    2014-01-01

    Synopsis This article reviews the recent literature regarding bone health as it relates to the patient living with neuromuscular disease (NMD). Poor bone health with related morbidity is a significant problem for patients with NMD. Although the evidence addressing issues of bone health and osteoporosis have increased as a result of the Bone and Joint Decade, studies defining the scope of bone-related disease in NMD are scant. The available evidence is discussed focusing on abnormal calcium metabolism, increased fracture risk, and the prevalence of both scoliosis and hypovitaminosis D in Duchenne muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy. These problems appear common. Osteomalacia often complicates disease-related baseline osteoporosis and may reduce fracture risk if treated. Future directions are discussed, including the urgent need for studies to both determine the nature and extent of poor bone health, and to evaluate the therapeutic effect of available osteoporosis treatments in patients with NMD. PMID:23137737

  1. Neuromuscular Electrical Stimulation Therapy for Dysphagia Caused by Wilson's Disease

    PubMed Central

    Lee, Seon Yeong; Yang, Hee Seung; Lee, Seung Hwa; Jeung, Hae Won; Park, Young Ok

    2012-01-01

    Wilson's disease is an autosomal recessive disorder of abnormal copper metabolism. Although dysphagia is a common complaint of patients with Wilson's disease and pneumonia is an important cause of death in these patients, management of swallowing function has rarely been reported in the context of Wilson's disease. Hence, we report a case of Wilson's disease presenting with dysphagia. A 33-year-old man visited our hospital with a complaint of difficulty in swallowing, since about last 7 years and which had worsened since the last 2-3 months. He was diagnosed with Wilson's disease about 13 years ago. On the initial VFSS, reduced hyoid bone movement, impaired epiglottic movement and moderate amount of residue in the valleculae during the pharyngeal phase were noted. After 10 sessions of neuromuscular electrical stimulation for 1 hour per day, decreased amount of residue was observed in the valleculae during the pharyngeal phase on the follow-up VFSS. PMID:22837979

  2. Presynaptic elements involved in the maintenance of the neuromuscular junction

    NASA Technical Reports Server (NTRS)

    Burrows, G. H.

    1984-01-01

    Alterations in the neuromuscular junction were observed in rats preceding loss of muscle mass. In view of the possibility that these alterations involve changes in the secretion of myotrophic agents by presynaptic motor neurons, an investigation was undertaken to characterize a neuronall factor which is thought to be involved in the initiation and maintenance of cholinergic synapses. This factor, which is secreted into the incubation medium by NG108-15 neuroblastoma x glioma hybrid cells, induces the aggregation of nicotinic acetylcholine receptors on primary cultures of rat hindlimb myotubes. Previous attempts to purify this factor failed. Extensive washing of the NG108-15 cells with hepes-buffered salt solution followed by short (4 hour) collection times resulted in the collection of incubation medium containing maximal aggregation activity with as little as 5 ug secreted protein per ml of fresh medium. A three-fold increase in specific activity was obtained after anion exchange chromatography.

  3. C57BL/6 Neuromuscular Healthspan Scoring System

    PubMed Central

    2013-01-01

    Developing a scoring system based on physiological and functional measurements is critical to test the efficacy of potential interventions for sarcopenia and frailty in aging animal models; therefore, the aim of this study was to develop a neuromuscular healthspan scoring system (NMHSS). We examined three ages of male C57BL/6 mice: adults (6–7 months old, 100% survival), old (24–26 months old, 75% survival), and elderly group (>28 months old, ≤50% survival)—as well as mice along this age continuum. Functional performance (as determined by the rotarod and inverted-cling grip test) and in vitro muscle contractility were the determinants. A raw score was derived for each determinant, and the NMHSS was then derived as the sum of the individual determinant scores. In comparison with individual determinants, the NMHSS reduced the effect of individual variability within age groups, thus potentially providing an enhanced ability to detect treatment effects in future studies. PMID:23585418

  4. A novel synaptic plasticity rule explains homeostasis of neuromuscular transmission

    PubMed Central

    Ouanounou, Gilles; Baux, Gérard; Bal, Thierry

    2016-01-01

    Excitability differs among muscle fibers and undergoes continuous changes during development and growth, yet the neuromuscular synapse maintains a remarkable fidelity of execution. Here we show in two evolutionarily distant vertebrates (Xenopus laevis cell culture and mouse nerve-muscle ex-vivo) that the skeletal muscle cell constantly senses, through two identified calcium signals, synaptic events and their efficacy in eliciting spikes. These sensors trigger retrograde signal(s) that control presynaptic neurotransmitter release, resulting in synaptic potentiation or depression. In the absence of spikes, synaptic events trigger potentiation. Once the synapse is sufficiently strong to initiate spiking, the occurrence of these spikes activates a negative retrograde feedback. These opposing signals dynamically balance the synapse in order to continuously adjust neurotransmitter release to a level matching current muscle cell excitability. DOI: http://dx.doi.org/10.7554/eLife.12190.001 PMID:27138195

  5. Endocannabinoids mediate muscarine-induced synaptic depression at the vertebrate neuromuscular junction.

    PubMed

    Newman, Zachary; Malik, Priya; Wu, Tse-Yu; Ochoa, Christopher; Watsa, Nayantara; Lindgren, Clark

    2007-03-01

    Endocannabinoids (eCBs) inhibit neurotransmitter release throughout the central nervous system. Using the Ceratomandibularis muscle from the lizard Anolis carolinensis we asked whether eCBs play a similar role at the vertebrate neuromuscular junction. We report here that the CB(1) cannabinoid receptor is concentrated on motor terminals and that eCBs mediate the inhibition of neurotransmitter release induced by the activation of M(3) muscarinic acetylcholine (ACh) receptors. N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide, a CB(1) antagonist, prevents muscarine from inhibiting release and arachidonylcyclopropylamide (ACPA), a CB(1) receptor agonist, mimics M(3) activation and occludes the effect of muscarine. As for its mechanism of action, ACPA reduces the action-potential-evoked calcium transient in the nerve terminal and this decrease is more than sufficient to account for the observed inhibition of neurotransmitter release. Similar to muscarine, the inhibition of synaptic transmission by ACPA requires nitric oxide, acting via the synthesis of cGMP and the activation of cGMP-dependent protein kinase. 2-Arachidonoylglycerol (2-AG) is responsible for the majority of the effects of eCB as inhibitors of phospholipase C and diacylglycerol lipase, two enzymes responsible for synthesis of 2-AG, significantly limit muscarine-induced inhibition of neurotransmitter release. Lastly, the injection of (5Z,8Z,11Z,14Z)-N-(4-hydroxy-2-methylphenyl)-5,8,11,14-eicosatetraenamide (an inhibitor of eCB transport) into the muscle prevents muscarine, but not ACPA, from inhibiting ACh release. These results collectively lead to a model of the vertebrate neuromuscular junction whereby 2-AG mediates the muscarine-induced inhibition of ACh release. To demonstrate the physiological relevance of this model we show that the CB(1) antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide prevents

  6. Effects of neuromuscular lags on controlling contact transitions

    PubMed Central

    Venkadesan, Madhusudhan; Valero-Cuevas, Francisco J.

    2009-01-01

    We present a numerical exploration of contact transitions with the fingertip. When picking up objects our fingertips must make contact at specific locations, and—upon contact—maintain posture while producing well-directed force vectors. However, the joint torques for moving the fingertip towards a surface (τm) are different from those for producing static force vectors (τf). We previously described the neural control of such abrupt transitions in humans, and found that unavoidable errors arise because sensorimotor time delays and lags prevent an instantaneous switch between different torques. Here, we use numerical optimization on a finger model to reveal physical bounds for controlling such rapid contact transitions. Resembling human data, it is necessary to anticipatorily switch joint torques to τf at about 30 ms before contact to minimize the initial misdirection of the fingertip force vector. This anticipatory strategy arises in our deterministic model from neuromuscular lags, and not from optimizing for robustness to noise/uncertainties. Importantly, the optimal solution also leads to a trade-off between the speed of force magnitude increase versus the accuracy of initial force direction. This is an alternative to prevailing theories that propose multiplicative noise in muscles as the driver of speed–accuracy trade-offs. We instead find that the speed–accuracy trade-off arises solely from neuromuscular lags. Finally, because our model intentionally uses idealized assumptions, its agreement with human data suggests that the biological system is controlled in a way that approaches the physical boundaries of performance. PMID:19218157

  7. Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome.

    PubMed

    Rowe, Peter C; Fontaine, Kevin R; Lauver, Megan; Jasion, Samantha E; Marden, Colleen L; Moni, Malini; Thompson, Carol B; Violand, Richard L

    2016-01-01

    Chronic fatigue syndrome (CFS) is a complex, multisystem disorder that can be disabling. CFS symptoms can be provoked by increased physical or cognitive activity, and by orthostatic stress. In preliminary work, we noted that CFS symptoms also could be provoked by application of longitudinal neural and soft tissue strain to the limbs and spine of affected individuals. In this study we measured the responses to a straight leg raise neuromuscular strain maneuver in individuals with CFS and healthy controls. We randomly assigned 60 individuals with CFS and 20 healthy controls to either a 15 minute period of passive supine straight leg raise (true neuromuscular strain) or a sham straight leg raise. The primary outcome measure was the symptom intensity difference between the scores during and 24 hours after the study maneuver compared to baseline. Fatigue, body pain, lightheadedness, concentration difficulties, and headache scores were measured individually on a 0-10 scale, and summed to create a composite symptom score. Compared to individuals with CFS in the sham strain group, those with CFS in the true strain group reported significantly increased body pain (P = 0.04) and concentration difficulties (P = 0.02) as well as increased composite symptom scores (all P = 0.03) during the maneuver. After 24 hours, the symptom intensity differences were significantly greater for the CFS true strain group for the individual symptom of lightheadedness (P = 0.001) and for the composite symptom score (P = 0.005). During and 24 hours after the exposure to the true strain maneuver, those with CFS had significantly higher individual and composite symptom intensity changes compared to the healthy controls. We conclude that a longitudinal strain applied to the nerves and soft tissues of the lower limb is capable of increasing symptom intensity in individuals with CFS for up to 24 hours. These findings support our preliminary observations that increased mechanical sensitivity may be a

  8. Systemic inflammatory response and neuromuscular involvement in amyotrophic lateral sclerosis

    PubMed Central

    Lu, Ching-Hua; Allen, Kezia; Oei, Felicia; Leoni, Emanuela; Kuhle, Jens; Tree, Timothy; Fratta, Pietro; Sharma, Nikhil; Sidle, Katie; Howard, Robin; Orrell, Richard; Fish, Mark; Greensmith, Linda; Pearce, Neil; Gallo, Valentina

    2016-01-01

    Objective: To evaluate the combined blood expression of neuromuscular and inflammatory biomarkers as predictors of disease progression and prognosis in amyotrophic lateral sclerosis (ALS). Methods: Logistic regression adjusted for markers of the systemic inflammatory state and principal component analysis were carried out on plasma levels of creatine kinase (CK), ferritin, and 11 cytokines measured in 95 patients with ALS and 88 healthy controls. Levels of circulating biomarkers were used to study survival by Cox regression analysis and correlated with disease progression and neurofilament light chain (NfL) levels available from a previous study. Cytokines expression was also tested in blood samples longitudinally collected for up to 4 years from 59 patients with ALS. Results: Significantly higher levels of CK, ferritin, tumor necrosis factor (TNF)–α, and interleukin (IL)–1β, IL-2, IL-8, IL-12p70, IL-4, IL-5, IL-10, and IL-13 and lower levels of interferon (IFN)–γ were found in plasma samples from patients with ALS compared to controls. IL-6, TNF-α, and IFN-γ were the most highly regulated markers when all explanatory variables were jointly analyzed. High ferritin and IL-2 levels were predictors of poor survival. IL-5 levels were positively correlated with CK, as was TNF-α with NfL. IL-6 was strongly associated with CRP levels and was the only marker showing increasing expression towards end-stage disease in the longitudinal analysis. Conclusions: Neuromuscular pathology in ALS involves the systemic regulation of inflammatory markers mostly active on T-cell immune responses. Disease stratification based on the prognostic value of circulating inflammatory markers could improve clinical trials design in ALS. PMID:27308305

  9. Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome

    PubMed Central

    Rowe, Peter C.; Fontaine, Kevin R.; Lauver, Megan; Jasion, Samantha E.; Marden, Colleen L.; Moni, Malini; Thompson, Carol B.; Violand, Richard L.

    2016-01-01

    Chronic fatigue syndrome (CFS) is a complex, multisystem disorder that can be disabling. CFS symptoms can be provoked by increased physical or cognitive activity, and by orthostatic stress. In preliminary work, we noted that CFS symptoms also could be provoked by application of longitudinal neural and soft tissue strain to the limbs and spine of affected individuals. In this study we measured the responses to a straight leg raise neuromuscular strain maneuver in individuals with CFS and healthy controls. We randomly assigned 60 individuals with CFS and 20 healthy controls to either a 15 minute period of passive supine straight leg raise (true neuromuscular strain) or a sham straight leg raise. The primary outcome measure was the symptom intensity difference between the scores during and 24 hours after the study maneuver compared to baseline. Fatigue, body pain, lightheadedness, concentration difficulties, and headache scores were measured individually on a 0–10 scale, and summed to create a composite symptom score. Compared to individuals with CFS in the sham strain group, those with CFS in the true strain group reported significantly increased body pain (P = 0.04) and concentration difficulties (P = 0.02) as well as increased composite symptom scores (all P = 0.03) during the maneuver. After 24 hours, the symptom intensity differences were significantly greater for the CFS true strain group for the individual symptom of lightheadedness (P = 0.001) and for the composite symptom score (P = 0.005). During and 24 hours after the exposure to the true strain maneuver, those with CFS had significantly higher individual and composite symptom intensity changes compared to the healthy controls. We conclude that a longitudinal strain applied to the nerves and soft tissues of the lower limb is capable of increasing symptom intensity in individuals with CFS for up to 24 hours. These findings support our preliminary observations that increased mechanical sensitivity may be a

  10. Development of Drosophila larval neuromuscular junctions: maintaining synaptic strength.

    PubMed

    Li, H; Peng, X; Cooper, R L

    2002-01-01

    In spite of the available information about the development of Drosophila neuromuscular junctions, the correlation between nerve terminal morphology and maintenance of synaptic strength has still not been systematically addressed throughout larval development. We characterized the growth of the abdominal longitudinal muscle 6 (m6) and the motor terminals Ib and Is that innervate it within segment 4. In addition, we measured the evoked excitatory junction potential (EJP) amplitudes while the Ib and Is axons were selectively recruited. Regression analysis with natural log transformation of response variables indicated that the developmental curves for m6 and the motor axons Ib and Is were best fitted as second order polynomial regressions during larval development. Initially Is terminals are longer and possess more synaptic varicosities at the first instar stage. The Is terminals also grow faster in subsequent developmental stages. The growth of nerve terminals and their target m6 are not proportional although tightly correlated. This results in a larger average muscle area innervated by a single varicosity as the animal develops. The amplitudes of the EJPs of Ib and Is neurons show no developmental difference in their amplitudes from the first to the late third larval instar. The Is axon consistently produced larger EJPs than the Ib axon at each developmental stage. The time constants for both rising and decay phases of EJPs increase exponentially throughout larval development. The results presented not only help in quantifying the normal development of Drosophila neuromuscular junctions, but also provide a framework for future investigations to properly interpret developmental abnormalities that may occur in various mutants. PMID:12421617

  11. Glutamatergic postsynaptic block by Pamphobeteus spider venoms in crayfish.

    PubMed

    Araque, A; Ferreira, W; Lucas, S; Buño, W

    1992-01-31

    The effects of toxins from venom glands of two south american spiders (Pamphobeteus platyomma and P. soracabae) on glutamatergic excitatory synaptic transmission were studied in the neuromuscular junction of the opener muscle of crayfish. The toxins selectively and reversibly blocked both excitatory postsynaptic currents and potentials in a dose-dependent manner. They also reversibly abolished glutamate-induced postsynaptic membrane depolarization. They had no effect on resting postsynaptic membrane conductance nor on postsynaptic voltage-gated currents. The synaptic facilitation and the frequency of miniature postsynaptic potentials were unaffected by the toxins, indicating that presynaptic events were not modified. Picrotoxin, a selective antagonist of the gamma-aminobutyric acid (GABA)A receptor, did not modify toxin effects. We conclude that both toxins specifically block the postsynaptic glutamate receptor-channel complex. PMID:1319261

  12. Testing block subdivision algorithms on block designs

    NASA Astrophysics Data System (ADS)

    Wiseman, Natalie; Patterson, Zachary

    2016-01-01

    Integrated land use-transportation models predict future transportation demand taking into account how households and firms arrange themselves partly as a function of the transportation system. Recent integrated models require parcels as inputs and produce household and employment predictions at the parcel scale. Block subdivision algorithms automatically generate parcel patterns within blocks. Evaluating block subdivision algorithms is done by way of generating parcels and comparing them to those in a parcel database. Three block subdivision algorithms are evaluated on how closely they reproduce parcels of different block types found in a parcel database from Montreal, Canada. While the authors who developed each of the algorithms have evaluated them, they have used their own metrics and block types to evaluate their own algorithms. This makes it difficult to compare their strengths and weaknesses. The contribution of this paper is in resolving this difficulty with the aim of finding a better algorithm suited to subdividing each block type. The proposed hypothesis is that given the different approaches that block subdivision algorithms take, it's likely that different algorithms are better adapted to subdividing different block types. To test this, a standardized block type classification is used that consists of mutually exclusive and comprehensive categories. A statistical method is used for finding a better algorithm and the probability it will perform well for a given block type. Results suggest the oriented bounding box algorithm performs better for warped non-uniform sites, as well as gridiron and fragmented uniform sites. It also produces more similar parcel areas and widths. The Generalized Parcel Divider 1 algorithm performs better for gridiron non-uniform sites. The Straight Skeleton algorithm performs better for loop and lollipop networks as well as fragmented non-uniform and warped uniform sites. It also produces more similar parcel shapes and patterns.

  13. Motor neuron apoptosis and neuromuscular junction perturbation are prominent features in a Drosophila model of Fus-mediated ALS

    PubMed Central

    2012-01-01

    Backgound Amyotrophic lateral sclerosis (ALS) is progressive neurodegenerative disease characterized by the loss of motor function. Several ALS genes have been identified as their mutations can lead to familial ALS, including the recently reported RNA-binding protein fused in sarcoma (Fus). However, it is not clear how mutations of Fus lead to motor neuron degeneration in ALS. In this study, we present a Drosophila model to examine the toxicity of Fus, its Drosophila orthologue Cabeza (Caz), and the ALS-related Fus mutants. Results Our results show that the expression of wild-type Fus/Caz or FusR521G induced progressive toxicity in multiple tissues of the transgenic flies in a dose- and age-dependent manner. The expression of Fus, Caz, or FusR521G in motor neurons significantly impaired the locomotive ability of fly larvae and adults. The presynaptic structures in neuromuscular junctions were disrupted and motor neurons in the ventral nerve cord (VNC) were disorganized and underwent apoptosis. Surprisingly, the interruption of Fus nuclear localization by either deleting its nuclear localization sequence (NLS) or adding a nuclear export signal (NES) blocked Fus toxicity. Moreover, we discovered that the loss of caz in Drosophila led to severe growth defects in the eyes and VNCs, caused locomotive disability and NMJ disruption, but did not induce apoptotic cell death. Conclusions These data demonstrate that the overexpression of Fus/Caz causes in vivo toxicity by disrupting neuromuscular junctions (NMJs) and inducing apoptosis in motor neurons. In addition, the nuclear localization of Fus is essential for Fus to induce toxicity. Our findings also suggest that Fus overexpression and gene deletion can cause similar degenerative phenotypes but the underlying mechanisms are likely different. PMID:22443542

  14. Interaction between protein kinase C and protein kinase A can modulate transmitter release at the rat neuromuscular synapse.

    PubMed

    Santafé, M M; Garcia, N; Lanuza, M A; Tomàs, M; Tomàs, J

    2009-02-15

    We used intracellular recording to investigate the functional interaction between protein kinase C (PKC) and protein kinase A (PKA) signal transduction cascades in the control of transmitter release in the neuromuscular synapses from adult rats. Our results indicate that: 1) PKA and PKC are independently involved in asynchronous release. 2) Evoked acetylcholine (ACh) release is enhanced with the PKA agonist Sp-8-BrcAMP and the PKC agonist phorbol ester (PMA). 3) PKA has a constitutive role in promoting a component of normal evoked transmitter release because, when the kinase is inhibited with H-89, the release diminishes. However, the PKC inhibitor calphostin C (CaC) does not affect ACh release. 4) PKA regulates neurotransmission without PKC involvement because, after PMA or CaC modulation of the PKC activity, coupling to the ACh release of PKA can normally be stimulated with Sp-8-BrcAMP or inhibited with H-89. 5) After PKA inhibition with H-89, PKC stimulation with PMA (or inhibition with CaC) does not lead to any change in evoked ACh release. However, in PKA-stimulated preparations with Sp-8-BrcAMP, PKC becomes tonically active, thus potentiating a component of release that can now be blocked with CaC. In normal conditions, therefore, PKA was able to modulate ACh release independently of PKC activity, whereas PKA stimulation caused the PKC coupling to evoked release. In contrast, PKA inhibition prevent PKC stimulation (with the phorbol ester) and coupling to ACh output. There was therefore some dependence of PKC on PKA activity in the fine control of the neuromuscular synaptic functionalism and ACh release. PMID:18816790

  15. The epidemiology of neuromuscular disorders: Age at onset and gender in the Netherlands.

    PubMed

    Deenen, Johanna C W; van Doorn, Pieter A; Faber, Catharina G; van der Kooi, Anneke J; Kuks, Jan B M; Notermans, Nicolette C; Visser, Leo H; Horlings, Corinne G C; Verschuuren, Jan J G M; Verbeek, André L M; van Engelen, Baziel G M

    2016-07-01

    Based on approximately eight years of data collection with the nationwide Computer Registry of All Myopathies and Polyneuropathies (CRAMP) in the Netherlands, recent epidemiologic information for thirty neuromuscular disorders is presented. This overview includes age and gender data for a number of neuromuscular disorders that are either relatively frequently seen in the neuromuscular clinic, or have a particular phenotype. Since 2004, over 20,000 individuals with a neuromuscular disorder were registered in CRAMP; 56% men and 44% women. The number per diagnosis varied from nine persons with Emery-Dreifuss muscular dystrophy to 2057 persons with amyotrophic lateral sclerosis. Proportions of men ranged from 38% with post-polio syndrome to 68% with progressive spinal muscular atrophy, excluding X-chromosome linked disorders. Inclusion body myositis showed the highest median age at diagnosis of 70 years. These data may be helpful in the diagnostic process in clinical practice and trial readiness. PMID:27212207

  16. Impaired voluntary neuromuscular activation limits muscle power in mobility-limited older adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background. Age-related alterations of neuromuscular activation may contribute to deficits in muscle power and mobility function. This study assesses whether impaired activation of the agonist quadriceps and antagonist hamstrings, including amplitude- and velocity-dependent characteristics of activa...

  17. Neuromuscular activity of Bothrops alcatraz snake venom in chick biventer cervicis preparations.

    PubMed

    de Moraes, Delkia Seabra; Aparecido de Abreu, Valdemir; Rostelato-Ferreira, Sandro; Leite, Gildo B; Alice da Cruz-Höfling, Maria; Travaglia-Cardoso, Silvia R; Hyslop, Stephen; Rodrigues-Simioni, Léa

    2012-02-01

    Venom (10-100 μg/ml) from Bothrops alcatraz, a pitviper from the Alcatrazes Archipelago off the coast of southeastern Brazil, caused progressive, irreversible neuromuscular blockade in chick isolated biventer cervicis preparations. The venom also inhibited contractures to exogenous ACh (110 μM) and KCl (20 mM), caused myofiber damage and increased creatine kinase release. Commercial bothropic antivenom raised against mainland Bothrops species neutralized the neuromuscular activity, depending on the venom concentration. PMID:22155137

  18. Physical complications in anorexia nervosa. Haematological and neuromuscular changes in 12 patients.

    PubMed

    Alloway, R; Shur, E; Obrecht, R; Russell, G F

    1988-07-01

    Of twelve patients consecutively admitted to the Maudsley Hospital Eating Disorders Unit, four had neuromuscular abnormality, eight haematological abnormality, and four no abnormality. All those having neuromuscular signs had concomitant haematological dysfunction. Vomiting, and food restriction with vegetarianism, appeared more likely to lead to complications than either food restriction alone or laxative abuse. The physical status of severely underweight patients admitted for refeeding needs to be carefully monitored. PMID:3224253

  19. Role of membrane cholesterol in spontaneous exocytosis at frog neuromuscular synapses: reactive oxygen species–calcium interplay

    PubMed Central

    Petrov, Alexey M; Yakovleva, Anastasiya A; Zefirov, Andrey L

    2014-01-01

    Using electrophysiological and optical techniques, we studied the mechanisms by which cholesterol depletion stimulates spontaneous transmitter release by exocytosis at the frog neuromuscular junction. We found that methyl-β-cyclodextrin (MCD, 10 mm)-mediated exhaustion of cholesterol resulted in the enhancement of reactive oxygen species (ROS) production, which was prevented by the antioxidant N-acetyl cysteine (NAC) and the NADPH oxidase inhibitor apocynin. An increase in ROS levels occurred both extra- and intracellularly, and it was associated with lipid peroxidation in synaptic regions. Cholesterol depletion provoked a rise in the intracellular Ca2+ concentration, which was diminished by NAC and transient receptor potential vanilloid (TRPV) channel blockers (ruthenium red and capsazepine). By contrast, the MCD-induced rise in [Ca2+]i remained unaffected if Ca2+ release from endoplasmic stores was blocked by TMB8 (8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride). The effects of cholesterol depletion on spontaneous release and exocytosis were significantly reduced by the antioxidant, intracellular Ca2+ chelation with BAPTA-AM and blockers of TRPV channels. Bath application of the calcineurin antagonist cyclosporine A blocked MCD-induced enhancement of spontaneous release/exocytosis, whereas okadaic acid, an inhibitor of phosphatases PP1 and PP2A, had no effect. Thus, our findings indicate that enhancement of spontaneous exocytosis induced by cholesterol depletion may depend on ROS generation, leading to an influx of Ca2+ via TRPV channels and, subsequently, activation of calcineurin. PMID:25326454

  20. Presynaptic and postsynaptic effects of the venom of the Australian tiger snake at the neuromuscular junction

    PubMed Central

    Datyner, M. E.; Gage, P. W.

    1973-01-01

    1. Crude venom (TSV) from the Australian tiger snake (Notechis scutatus scutatus) has both presynaptic and postsynaptic effects at the neuromuscular junctions of toads. 2. TSV (50 μg/ml) rapidly blocked indirectly elicited muscle twitches without affecting the compound action potential in the sciatic nerve or twitches elicited by direct stimulation. 3. Low concentrations of the venom (1-10 μg/ml) reduced the amplitude of miniature endplate potentials (m.e.p.ps) and inhibited the depolarization of muscle fibres normally caused by carbachol. It was concluded that a fraction of the venom binds to acetylcholine receptors. 4. The frequency of m.e.p.ps was at first increased by TSV at a concentration of 1 μg/ml. Occasional, high frequency `bursts' of m.e.p.ps were recorded in some preparations. The mean frequency of m.e.p.ps appeared to fall after several hours in the venom. 5. The quantal content of endplate potentials (e.p.ps) was reduced by the venom. With low concentrations (1 μg/ml), an initial increase in quantal content was often seen. When the quantal content was markedly depressed there was no parallel reduction in the amplitude of nerve terminal spikes recorded extracellularly, though a later fall in size and slowing of time course was often seen. 6. There was evidence that TSV eventually changed the normal Poisson characteristics of the spontaneous release of quanta and this may be correlated with electronmicroscopic changes in nerve terminals. 7. Tiger snake antivenene counteracted the postsynaptic, but not the presynaptic effects of TSV when they had developed. PMID:4367126

  1. Neuromuscular Junction Formation in Tissue-Engineered Skeletal Muscle Augments Contractile Function and Improves Cytoskeletal Organization

    PubMed Central

    Martin, Neil R.W.; Passey, Samantha L.; Player, Darren J.; Mudera, Vivek; Baar, Keith; Greensmith, Linda

    2015-01-01

    Neuromuscular and neurodegenerative diseases are conditions that affect both motor neurons and the underlying skeletal muscle tissue. At present, the majority of neuromuscular research utilizes animal models and there is a growing need to develop novel methodologies that can be used to help understand and develop treatments for these diseases. Skeletal muscle tissue-engineered constructs exhibit many of the characteristics of the native tissue such as accurate fascicular structure and generation of active contractions. However, to date, there has been little consideration toward the integration of engineered skeletal muscle with motor neurons with the aim of neuromuscular junction (NMJ) formation, which would provide a model to investigate neuromuscular diseases and basic biology. In the present work we isolated primary embryonic motor neurons and neonatal myoblasts from Sprague-Dawley rats, and cocultured the two cell types in three-dimensional tissue-engineered fibrin hydrogels with the aim of NMJ formation. Immunohistochemistry revealed myotube formation in a fascicular arrangement and neurite outgrowth from motor neuron cell bodies toward the aligned myotubes. Furthermore, colocalization of pre- and postsynaptic proteins and chemical inhibition of spontaneous myotube twitch indicated the presence of NMJs in the innervated constructs. When electrical field stimulation was employed to evoke isometric contractions, maximal twitch and tetanic force were higher in the constructs cocultured with motor neurons, which may, in part, be explained by improved myotube cytoskeletal organization in these constructs. The fabrication of such constructs may be useful tools for investigating neuromuscular pharmaceuticals and improving the understanding of neuromuscular pathologies. PMID:26166548

  2. Appropriate dosing of sugammadex to reverse deep rocuronium-induced neuromuscular blockade in morbidly obese patients.

    PubMed

    Loupec, T; Frasca, D; Rousseau, N; Faure, J-P; Mimoz, O; Debaene, B

    2016-03-01

    In morbidly obese patients, the speed of reversal of neuromuscular blockade with sugammadex based on ideal body weight is still matter of debate. In this single-center, randomised, double-blinded study, neuromuscular blockade was monitored in 50 patients using acceleromyography at the adductor pollicis. At the end of surgery with deep rocuronium-induced neuromuscular blockade, patients randomly received sugammadex 4 mg.kg(-1) (high dose group), 2 mg.kg(-1) (middle dose group), or 1 mg.kg(-1) (low dose group) of ideal body weight. After administration of the first dose of sugammadex, the mean (SD) recovery time (censored at 600 s) from deep neuromuscular blockade was significantly shorter (p < 0.001) in the high-dose group (n = 14; 255 (63) s) vs the middle-dose group (n = 13; 429 (102) s), or low-dose group (n = 4; 581 (154) s). Success rate from neuromuscular blockade reversal defined by a train-of-four ≥ 0.9 within 10 min after sugammadex administration, were 93%, 77% and 22% for these high, middle and low-dose groups respectively (p < 0.05 vs low-dose group). In morbidly obese patients, 4 mg.kg(-1) of ideal body weight of sugammadex allows suitable reversal of deep rocuronium-induced neuromuscular blockade. Monitoring remains essential to detect residual curarisation or recurarisation. PMID:26685122

  3. Routine and specialized laboratory testing for the diagnosis of neuromuscular diseases in dogs and cats.

    PubMed

    Shelton, G Diane

    2010-09-01

    The diagnosis of neuromuscular diseases can be challenging. The first step is recognition that the disease involves the neuromuscular system (muscle, neuromuscular junction, peripheral nerve, and ventral horn cells of the spinal cord). Many neuromuscular diseases share clinical signs and cannot be distinguished based on clinical examination. Routine laboratory screening, including a CBC, biochemical profile, and urinalysis, can identify some of the most common systemic abnormalities that cause muscle weakness and myalgia, such as hypo- and hyperglycemia, electrolyte disorders, or thyroid abnormalities, and may suggest a specific diagnosis, such as diabetes mellitus, hypo- or hyperadrenocorticism, renal failure, or hypothyroidism. Increased creatine kinase activity, increased cardiac troponin I concentration, and myoglobinuria are useful in detecting skeletal and cardiac muscle damage. Identification of acetylcholine receptor antibodies is diagnostic for acquired myasthenia gravis. For primary muscle or peripheral nerve diseases, tissue biopsy is the most direct way to determine specific pathology, correctly classify the disease, and determine the course of additional laboratory testing. For example, inflammatory, necrotizing, dystrophic, metabolic, or congenital myopathies require different laboratory testing procedures for further characterization. Many neuromuscular diseases are inherited or breed-associated, and DNA-based tests may already be established or may be feasible to develop after the disorder has been accurately characterized. This review focuses on both routine and specialized laboratory testing necessary to reach a definitive diagnosis and determine an accurate prognosis for neuromuscular diseases. PMID:20726955

  4. Effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction.

    PubMed

    Shim, Jae-Kwang; Choi, Ho-Suk; Shin, Jun-Ho

    2015-12-01

    [Purpose] This study examined the effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction. [Subjects and Methods] The subjects were 16 adults who underwent arthroscopic anterior cruciate reconstruction and neuromuscular training. The Lysholm scale was used to assess functional disorders on the affected knee joint. A KT-2000 arthrometer was used to measure anterior displacement of the tibia against the femur. Surface electromyography was used to detect the muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus before and after neuromuscular training. [Results] There was significant relaxation in tibial anterior displacement of the affected and sound sides in the supine position before neuromuscular training. Furthermore, the difference in the tibial anterior displacement of the affected knee joints in the standing position was reduced after neuromuscular training. Moreover, the variation of the muscle activation evoked higher muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus. [Conclusion] Neuromuscular training may improve functional joint stability in patients with orthopedic musculoskeletal injuries in the postoperative period. PMID:26834316

  5. Proprioceptive Neuromuscular Facilitation (PNF): Its Mechanisms and Effects on Range of Motion and Muscular Function

    PubMed Central

    Hindle, Kayla B.; Whitcomb, Tyler J.; Briggs, Wyatt O.; Hong, Junggi

    2012-01-01

    Proprioceptive neuromuscular facilitation (PNF) is common practice for increasing range of motion, though little research has been done to evaluate theories behind it. The purpose of this study was to review possible mechanisms, proposed theories, and physiological changes that occur due to proprioceptive neuromuscular facilitation techniques. Four theoretical mechanisms were identified: autogenic inhibition, reciprocal inhibition, stress relaxation, and the gate control theory. The studies suggest that a combination of these four mechanisms enhance range of motion. When completed prior to exercise, proprioceptive neuromuscular facilitation decreases performance in maximal effort exercises. When this stretching technique is performed consistently and post exercise, it increases athletic performance, along with range of motion. Little investigation has been done regarding the theoretical mechanisms of proprioceptive neuromuscular facilitation, though four mechanisms were identified from the literature. As stated, the main goal of proprioceptive neuromuscular facilitation is to increase range of motion and performance. Studies found both of these to be true when completed under the correct conditions. These mechanisms were found to be plausible; however, further investigation needs to be conducted. All four mechanisms behind the stretching technique explain the reasoning behind the increase in range of motion, as well as in strength and athletic performance. Proprioceptive neuromuscular facilitation shows potential benefits if performed correctly and consistently. PMID:23487249

  6. Effects of the potassium channel blocking dendrotoxins on acetylcholine release and motor nerve terminal activity.

    PubMed

    Anderson, A J; Harvey, A L

    1988-01-01

    1. The effects of the K+ channel blocking toxins, the dendrotoxins, on neuromuscular transmission and motor nerve terminal activity were assessed on frog cutaneous pectoris, mouse diaphragm and mouse triangularis sterni nerve-muscle preparations. Endplate potentials (e.p.ps) and miniature e.p.ps were recorded with intracellular microelectrodes, and nerve terminal spikes were recorded with extracellular electrodes placed in the perineural sheaths of motor nerves. 2. Dendrotoxin from green mamba (Dendroaspis angusticeps) venom and toxin I from black mamba (D. polylepis) venom increased the amplitude of e.p.ps by increasing quantal content, and also induced repetitive e.p.ps. 3. Perineural recordings revealed that dendrotoxins could decrease the component of the waveform associated with K+ currents at the nerve terminals, and induce repetitive activation of nerve terminals. 4. In frog motor nerves, dendrotoxins are known to block the fast f1 component of the K+ current at nodes of Ranvier. Blockade of a similar component of the K+ current at motor nerve terminals may be responsible for the effects of these toxins on neuromuscular transmission. 5. Similar conclusions can be drawn from the results obtained from mouse neuromuscular junctions. PMID:2450611

  7. Amplification of neuromuscular transmission by methylprednisolone involves activation of presynaptic facilitatory adenosine A2A receptors and redistribution of synaptic vesicles.

    PubMed

    Oliveira, L; Costa, A C; Noronha-Matos, J B; Silva, I; Cavalcante, W L G; Timóteo, M A; Corrado, A P; Dal Belo, C A; Ambiel, C R; Alves-do-Prado, W; Correia-de-Sá, P

    2015-02-01

    The mechanisms underlying improvement of neuromuscular transmission deficits by glucocorticoids are still a matter of debate despite these compounds have been used for decades in the treatment of autoimmune myasthenic syndromes. Besides their immunosuppressive action, corticosteroids may directly facilitate transmitter release during high-frequency motor nerve activity. This effect coincides with the predominant adenosine A2A receptor tonus, which coordinates the interplay with other receptors (e.g. muscarinic) on motor nerve endings to sustain acetylcholine (ACh) release that is required to overcome tetanic neuromuscular depression in myasthenics. Using myographic recordings, measurements of evoked [(3)H]ACh release and real-time video microscopy with the FM4-64 fluorescent dye, results show that tonic activation of facilitatory A2A receptors by endogenous adenosine accumulated during 50 Hz bursts delivered to the rat phrenic nerve is essential for methylprednisolone (0.3 mM)-induced transmitter release facilitation, because its effect was prevented by the A2A receptor antagonist, ZM 241385 (10 nM). Concurrent activation of the positive feedback loop operated by pirenzepine-sensitive muscarinic M1 autoreceptors may also play a role, whereas the corticosteroid action is restrained by the activation of co-expressed inhibitory M2 and A1 receptors blocked by methoctramine (0.1 μM) and DPCPX (2.5 nM), respectively. Inhibition of FM4-64 loading (endocytosis) by methylprednisolone following a brief tetanic stimulus (50 Hz for 5 s) suggests that it may negatively modulate synaptic vesicle turnover, thus increasing the release probability of newly recycled vesicles. Interestingly, bulk endocytosis was rehabilitated when methylprednisolone was co-applied with ZM241385. Data suggest that amplification of neuromuscular transmission by methylprednisolone may involve activation of presynaptic facilitatory adenosine A2A receptors by endogenous adenosine leading to synaptic

  8. Block That Pain!

    MedlinePlus

    ... combination produces a unique effect, blocking pain-sensing neurons without impairing signals from other cells. In contrast, ... surgical procedures block activity in all types of neurons. This can cause numbness, paralysis, and other nervous ...

  9. The effects of exercise training of different intensities on neuromuscular junction morphology.

    PubMed

    Deschenes, M R; Maresh, C M; Crivello, J F; Armstrong, L E; Kraemer, W J; Covault, J

    1993-08-01

    Little is known about the effects of exercise training on neuromuscular junction morphology in skeletal muscle. The objectives of this investigation were: 1) to determine if exercise training would elicit changes in neuromuscular junction morphology, 2) to determine if exercise training of different intensities would evoke specific changes in neuromuscular junction morphology, and 3) to determine whether changes in neuromuscular junction structure occur independently of changes in muscle fibre type and size. Twenty-four age and size matched male Sprague-Dawley rats were randomly assigned to three groups: high-intensity trained (HIT), low-intensity trained (LIT), or untrained. Neuromuscular junction morphology of the soleus muscle was determined via immunofluorescent staining. Presynaptic acetylcholine vesicles were visualized with SV-2 antibody in conjunction with fluorescein isothiocyanate labelled secondary secondary antibody. Postsynaptic acetylcholine receptors were identified with rhodamine labelled alpha-bungarotoxin. Laser scanning microscopy was used to produce images of synapses, which were used to quantitate the following: total area of SV-2 and alpha-bungarotoxin staining, density of acetylcholine vesicles and receptors, structural complexity, and synaptic coupling. To visualize nerve terminal branching, a smaller number of neuromuscular junctions were stained with C-2 antibody, which reacts with a neurofilament epitope, in conjunction with fluorescein isothiocyanate labelled secondary antibody. Total length of branching, number of branches, average length of branches, and ratio of secondary to primary branches per neuromuscular junction were determined. Citrate synthase activity, fibre type composition and fibre cross-sectional areas of the soleus muscle were assessed to determine the presence of a training effect in that muscle. Results indicate that training did induce hypertrophy of the neuromuscular junction that was independent of muscle

  10. The Block Scheduling Handbook.

    ERIC Educational Resources Information Center

    Queen, J. Allen

    Block scheduling encourages increased comprehensive immersion into subject matter, improved teacher-student relationships, and decreased disciplinary problems. While block scheduling may offer many advantages, moving to a block schedule from conventional scheduling can be a major adjustment for both students and teachers. This guide is intended to…

  11. Block Scheduling. Research Brief

    ERIC Educational Resources Information Center

    Muir, Mike

    2003-01-01

    What are the effects of block scheduling? Results of transitioning from traditional to block scheduling are mixed. Some studies indicate no change in achievement results, nor change in teachers' opinions about instructional strategies. Other studies show that block scheduling doesn't work well for Advanced Placement or Music courses, that "hard to…

  12. Efficacy of pulsed low-intensity electric neuromuscular stimulation in reducing pain and disability in patients with myofascial syndrome.

    PubMed

    Iodice, P; Lessiani, G; Franzone, G; Pezzulo, G

    2016-01-01

    Myofascial pain syndrome (MPS) is characterized by chronic pain in multiple myofascial trigger points and fascial constrictions. In recent years, the scientific literature has recognized the need to include the patient with MPS in a multidimensional rehabilitation project. At the moment, the most widely recognized therapeutic methods for the treatment of myofascial syndrome include the stretch and spray pressure massage. Microcurrent electric neuromuscular stimulation was proposed in pain management for its effects on normalizing bioelectricity of cells and for its sub-sensory application. In this study, we tested the efficacy of low-intensity pulsed electric neuromuscular stimulus (PENS) on pain in patients with MPS of cervical spine muscles. We carried out a prospective-analytic longitudinal study at an outpatient clinic during two weeks. Forty subjects (mean age 42±13 years) were divided into two groups: treatment (TrGr, n=20) and control group (CtrlGr, n=20). Visual-analog scale (VAS) values, concerning the spontaneous and movement-related pain in the cervical-dorsal region at baseline (T0) and at the end of the study (T1), showed a reduction from 7 to 3.81 (p < 0.001) in TrGr. In the CtrlGr, VAS was reduced from 8.2 to 7.2 (n.s.). Moreover, the pressure pain threshold at T0 was 2.1 vs 4.2 at T1 (p < 0.001) in TrG. In the CtrlGR we observed no significant changes. Modulated low-intensity PENS is an innovative therapy permitting to act on the transmission of pain and on the restoration of tissue homeostasis. It seems to affect the transmission of pain through the stimulation of A-beta fibers. The above results show that low-intensity PENS can be considered as an effective treatment to reduce pain and disability in patients with MPS. PMID:27358158

  13. Neuromuscular physiology of Hymenolepis diminuta and H. microstoma (Cestoda).

    PubMed

    Thompson, C S; Mettrick, D F

    1984-12-01

    The physiology of the neuromuscular systems in Hymenolepis diminuta and H. microstoma was studied in vitro using intact, adult worm and strips of worm body wall. Intact worms were insensitive to ionic changes in the in vitro buffering system. However, strips of body wall containing longitudinal muscles were extremely sensitive to ionic manipulation. In intact worms tension generated in the strobila had two components; small brief tension peaks up to 500 mg amplitude are superimposed on larger, longer peaks of up to 1200 mg amplitude. Removal of the scolex and neck region either failed to show significant changes in tension, or showed a reduction in amplitude but not of frequency. Muscle contraction of both H. diminuta and H. microstoma were qualitatively similar. In split-worm preparations the concentration of Ca2+ in the bathing solution significantly affected both spontaneous and evoked contractions in H. diminuta and H. microstoma; the addition of CaCl2 greatly reduced the amplitude and frequency of the contractions. The chloride salts of cobalt, barium, cadmium and manganese elicited prolonged contractions of the longitudinal musculature of both H. diminuta and H. microstoma. While CoCl2 was the most effective in stimulating muscle contraction, the magnitude of the response varied with the concentration of Ca2+ in the bath. The results indicate that peripheral inhibition is extremely important in cestode motor control and that extracellular calcium ions may regulate the peripheral inhibitory mechanisms. PMID:6440096

  14. Applications of Shape Memory Alloys for Neurology and Neuromuscular Rehabilitation

    PubMed Central

    Pittaccio, Simone; Garavaglia, Lorenzo; Ceriotti, Carlo; Passaretti, Francesca

    2015-01-01

    Shape memory alloys (SMAs) are a very promising class of metallic materials that display interesting nonlinear properties, such as pseudoelasticity (PE), shape memory effect (SME) and damping capacity, due to high mechanical hysteresis and internal friction. Our group has applied SMA in the field of neuromuscular rehabilitation, designing some new devices based on the mentioned SMA properties: in particular, a new type of orthosis for spastic limb repositioning, which allows residual voluntary movement of the impaired limb and has no predetermined final target position, but follows and supports muscular elongation in a dynamic and compliant way. Considering patients in the sub-acute phase after a neurological lesion, and possibly bedridden, the paper presents a mobiliser for the ankle joint, which is designed exploiting the SME to provide passive exercise to the paretic lower limb. Two different SMA-based applications in the field of neuroscience are then presented, a guide and a limb mobiliser specially designed to be compatible with diagnostic instrumentations that impose rigid constraints in terms of electromagnetic compatibility and noise distortion. Finally, the paper discusses possible uses of these materials in the treatment of movement disorders, such as dystonia or hyperkinesia, where their dynamic characteristics can be advantageous. PMID:26023790

  15. Neuromuscular diversity in archosaur deep dorsal thigh muscles.

    PubMed

    Gatesy, S M

    1994-01-01

    The living members of the clade Archosauria, crocodilians and birds, differ markedly in the morphology of their deep dorsal thigh muscles. To investigate whether this diversity is accompanied by differences in motor pattern and muscle function, the hindlimbs of representative archosaurs were studied by electromyography and cineradiography during terrestrial locomotion. In a crocodilian, Alligator, the iliofemoralis and pubo-ischio-femoralis internus part 2 are both active during the swing phase of the stride cycle. This appears to be the primitive motor pattern for archosaurs. There are four avian homologues of these muscles in the helmeted guineafowl, Numida. These are primarily active in the propulsive phase (iliotrochantericus caudalis and iliotrochantericus medius), the swing phase (iliotrochantericus cranialis) and a speed-dependent combination of the propulsive and/or swing phases (iliofemoralis externus). Differences between Alligator and Numida in the number and attachment of deep dorsal muscles are associated with dissimilar motor patterns and functions. Evolutionary modifications of neuromuscular control must be recognized when evaluating avian locomotor history, but are rarely considered by paleontologists. Even within the deep dorsal thigh muscles of Numida, developmentally and anatomically similar muscles are active out-of-phase. Therefore, although the actions of two adjacent muscles appear equivalent, their functions may differ dramatically. The diversity of deep dorsal thigh muscles in modern birds may be a good model for studying the relationship between activity pattern and peripheral morphology. PMID:8306187

  16. Safe neuromuscular electrical stimulator designed for the elderly.

    PubMed

    Krenn, Matthias; Haller, Michael; Bijak, Manfred; Unger, Ewald; Hofer, Christian; Kern, Helmut; Mayr, Winfried

    2011-03-01

    A stimulator for neuromuscular electrical stimulation (NMES) was designed, especially suiting the requirements of elderly people with reduced cognitive abilities and diminished fine motor skills. The aging of skeletal muscle is characterized by a progressive decline in muscle mass, force, and condition. Muscle training with NMES reduces the degradation process. The discussed system is intended for evoked muscle training of the anterior and posterior thigh. The core of the stimulator is based on a microcontroller with two modular output stages. The system has two charge-balanced biphasic voltage-controlled stimulation channels. Additionally, the evoked myoelectric signal (M-wave) and the myokinematic signal (surface acceleration) are measured. A central controller unit allows using the stimulator as a stand-alone device. To set up the training sequences and to evaluate the compliance data, a personal computer is connected to the stimulator via a universal serial bus. To help elderly people handle the stimulator by themselves, the user interface is kept very simple. For safety reasons, the electrode impedance is monitored during stimulation. A comprehensive compliance management with included measurements of muscle activity and stimulation intensity enables a scientific use of the stimulator in clinical trials. PMID:21401669

  17. Using factor analysis to identify neuromuscular synergies during treadmill walking

    NASA Technical Reports Server (NTRS)

    Merkle, L. A.; Layne, C. S.; Bloomberg, J. J.; Zhang, J. J.

    1998-01-01

    Neuroscientists are often interested in grouping variables to facilitate understanding of a particular phenomenon. Factor analysis is a powerful statistical technique that groups variables into conceptually meaningful clusters, but remains underutilized by neuroscience researchers presumably due to its complicated concepts and procedures. This paper illustrates an application of factor analysis to identify coordinated patterns of whole-body muscle activation during treadmill walking. Ten male subjects walked on a treadmill (6.4 km/h) for 20 s during which surface electromyographic (EMG) activity was obtained from the left side sternocleidomastoid, neck extensors, erector spinae, and right side biceps femoris, rectus femoris, tibialis anterior, and medial gastrocnemius. Factor analysis revealed 65% of the variance of seven muscles sampled aligned with two orthogonal factors, labeled 'transition control' and 'loading'. These two factors describe coordinated patterns of muscular activity across body segments that would not be evident by evaluating individual muscle patterns. The results show that factor analysis can be effectively used to explore relationships among muscle patterns across all body segments to increase understanding of the complex coordination necessary for smooth and efficient locomotion. We encourage neuroscientists to consider using factor analysis to identify coordinated patterns of neuromuscular activation that would be obscured using more traditional EMG analyses.

  18. Neuromuscular disorders: genes, genetic counseling and therapeutic trials.

    PubMed

    Zatz, Mayana; Passos-Bueno, Maria Rita; Vainzof, Mariz

    2016-01-01

    Neuromuscular disorders (NMD) are a heterogeneous group of genetic conditions, with autosomal dominant, recessive, or X-linked inheritance. They are characterized by progressive muscle degeneration and weakness. Here, we are presenting our major contributions to the field during the past 30 years. We have mapped and identified several novel genes responsible for NMD. Genotype-phenotype correlations studies enhanced our comprehension on the effect of gene mutations on related proteins and their impact on clinical findings. The search for modifier factors allowed the identification of a novel "protective"; variant which may have important implication on therapeutic developments. Molecular diagnosis was introduced in the 1980s and new technologies have been incorporated since then. Next generation sequencing greatly improved our capacity to identify disease-causing mutations with important benefits for research and prevention through genetic counseling of patients' families. Stem cells researches, from and for patients, have been used as tools to study human genetic diseases mechanisms and for therapies development. The clinical effect of preclinical trials in mice and canine models for muscular dystrophies are under investigation. Finally, the integration of our researches and genetic services with our post-graduation program resulted in a significant output of new geneticists, spreading out this expertise to our large country. PMID:27575431

  19. Neuromuscular disorders: genes, genetic counseling and therapeutic trials

    PubMed Central

    Zatz, Mayana; Passos-Bueno, Maria Rita; Vainzof, Mariz

    2016-01-01

    Abstract Neuromuscular disorders (NMD) are a heterogeneous group of genetic conditions, with autosomal dominant, recessive, or X-linked inheritance. They are characterized by progressive muscle degeneration and weakness. Here, we are presenting our major contributions to the field during the past 30 years. We have mapped and identified several novel genes responsible for NMD. Genotype-phenotype correlations studies enhanced our comprehension on the effect of gene mutations on related proteins and their impact on clinical findings. The search for modifier factors allowed the identification of a novel "protective"; variant which may have important implication on therapeutic developments. Molecular diagnosis was introduced in the 1980s and new technologies have been incorporated since then. Next generation sequencing greatly improved our capacity to identify disease-causing mutations with important benefits for research and prevention through genetic counseling of patients' families. Stem cells researches, from and for patients, have been used as tools to study human genetic diseases mechanisms and for therapies development. The clinical effect of preclinical trials in mice and canine models for muscular dystrophies are under investigation. Finally, the integration of our researches and genetic services with our post-graduation program resulted in a significant output of new geneticists, spreading out this expertise to our large country. PMID:27575431

  20. Peripheral nerve and neuromuscular junction pathology in Pompe disease

    PubMed Central

    Falk, Darin J.; Todd, Adrian Gary; Lee, Sooyeon; Soustek, Meghan S.; ElMallah, Mai K.; Fuller, David D.; Notterpek, Lucia; Byrne, Barry J.

    2015-01-01

    Pompe disease is a systemic metabolic disorder characterized by lack of acid-alpha glucosidase (GAA) resulting in ubiquitous lysosomal glycogen accumulation. Respiratory and ambulatory dysfunction are prominent features in patients with Pompe yet the mechanism defining the development of muscle weakness is currently unclear. Transgenic animal models of Pompe disease mirroring the patient phenotype have been invaluable in mechanistic and therapeutic study. Here, we demonstrate significant pathological alterations at neuromuscular junctions (NMJs) of the diaphragm and tibialis anterior muscle as prominent features of disease pathology in Gaa knockout mice. Postsynaptic defects including increased motor endplate area and fragmentation were readily observed in Gaa−/− but not wild-type mice. Presynaptic neuropathic changes were also evident, as demonstrated by significant reduction in the levels of neurofilament proteins, and alterations in axonal fiber diameter and myelin thickness within the sciatic and phrenic nerves. Our data suggest the loss of NMJ integrity is a primary contributor to the decline in respiratory and ambulatory function in Pompe and arises from both pre- and postsynaptic pathology. These observations highlight the importance of systemic phenotype correction, specifically restoration of GAA to skeletal muscle and the nervous system for treatment of Pompe disease. PMID:25217571

  1. Extracardiac medical and neuromuscular implications in restrictive cardiomyopathy.

    PubMed

    Stöllberger, Claudia; Finsterer, Josef

    2007-08-01

    Restrictive cardiomyopathy (RCMP) is characterized by restrictive filling and reduced diastolic volume of either or both ventricles with normal or near-normal systolic function and wall thickness. It may occur idiopathically or as a cardiac manifestation of systemic diseases such as scleroderma, amyloidosis, Churg-Strauss syndrome, cystinosis, sarcoidosis, lymphoma, Gaucher's disease, hemochromatosis, Fabry's disease, pseudoxanthoma elasticum, hypereosinophilic syndrome, carcinoid, Noonan's syndrome, reactive arthritis, or Werner's syndrome and various neuromuscular disorders. Whereas in idiopathic RCMP the therapeutic options are only treatment of cardiac congestion, in cases with an underlying disorder, a causal therapy may be available. Patients with RCMP should be investigated as soon as the cardiac diagnosis is established for extracardiac diseases to detect a possibly treatable cause of RCMP before the disease becomes intractable. These investigations include a diligent clinical history and examination, blood tests, and ophthalmologic, otologic, dermatologic, gastroenterologic, nephrologic, hematologic, and neurologic examinations. If extracardiac examinations do not reveal a plausible cause for RCMP, endomyocardial biopsy is indicated. PMID:17680617

  2. Development of neuromuscular organization in the ctenophore Pleurobrachia bachei.

    PubMed

    Norekian, Tigran P; Moroz, Leonid L

    2016-01-01

    The phylogenetic position of the phylum Ctenophora and the nature of ctenphore nervous systems are highly debated topics in modern evolutionary biology. However, very little is known about the organization of ctenophore neural and muscular systems, and virtually nothing has been reported about their embryogenesis. Here we have characterized the neural and muscular development of the sea gooseberry, Pleurobrachia bachei, starting from the cleavage stages to posthatching larvae. Scanning electron microscopy and immunochemistry were used to describe the formation of the embryonic mouth, tentacles, combs, aboral organ, and putative sensory cells. The muscles started their specification at the end of the first day of Pleurobrachia development. In contrast, neurons appeared 2 days after myogenesis, just before the hatching of fully formed cydippid larvae. The first tubulin-immunoreactive neurons, a small group of four to six cells with neuronal processes, was initially recognized at the aboral pole during the third day of development. Surprisingly, this observed neurogenesis occurred after the emergence of distinct behavioral patterns in the embryos. Thus, the embryonic behavior associated with comb cilia beatings and initial muscle organization does not require morphologically defined neurons and their elongated neurites. This study provides the first description of neuromuscular development in the enigmatic ctenophores and establishes the foundation for future research using emerging genomic tools and resources. PMID:26105692

  3. Applications of shape memory alloys for neurology and neuromuscular rehabilitation.

    PubMed

    Pittaccio, Simone; Garavaglia, Lorenzo; Ceriotti, Carlo; Passaretti, Francesca

    2015-01-01

    Shape memory alloys (SMAs) are a very promising class of metallic materials that display interesting nonlinear properties, such as pseudoelasticity (PE), shape memory effect (SME) and damping capacity, due to high mechanical hysteresis and internal friction. Our group has applied SMA in the field of neuromuscular rehabilitation, designing some new devices based on the mentioned SMA properties: in particular, a new type of orthosis for spastic limb repositioning, which allows residual voluntary movement of the impaired limb and has no predetermined final target position, but follows and supports muscular elongation in a dynamic and compliant way. Considering patients in the sub-acute phase after a neurological lesion, and possibly bedridden, the paper presents a mobiliser for the ankle joint, which is designed exploiting the SME to provide passive exercise to the paretic lower limb. Two different SMA-based applications in the field of neuroscience are then presented, a guide and a limb mobiliser specially designed to be compatible with diagnostic instrumentations that impose rigid constraints in terms of electromagnetic compatibility and noise distortion. Finally, the paper discusses possible uses of these materials in the treatment of movement disorders, such as dystonia or hyperkinesia, where their dynamic characteristics can be advantageous. PMID:26023790

  4. Effects of two neuromuscular fatigue protocols on landing performance.

    PubMed

    James, C Roger; Scheuermann, Barry W; Smith, Michael P

    2010-08-01

    The purpose of the study was to investigate the effects of two fatigue protocols on landing performance. A repeated measures design was used to examine the effects of fatigue and fatigue protocol on neuromuscular and biomechanical performance variables. Ten volunteers performed non-fatigued and fatigued landings on two days using different fatigue protocols. Repeated maximum isometric squats were used to induce fatigue on day one. Sub-maximum cycling was used to induce fatigue on day two. Isometric squat maximum voluntary contraction (MVC) was measured before and after fatigued landings on each day. During the landings, ground reaction force (GRF), knee kinematics, and electromyographic (EMG) data were recorded. Isometric MVC, GRF peaks, loading rates, impulse, knee flexion at contact, range of motion, max angular velocity, and EMG root mean square (RMS) values were compared pre- and post-fatiguing exercise and between fatigue protocols using repeated ANOVA. Fatigue decreased MVC strength (p0.05), GRF second peak, and initial impulse (p0.01), but increased quadriceps medium latency stretch reflex EMG activity (p0.012). Knee flexion at contact was 5.2 degrees greater (p0.05) during fatigued landings following the squat exercise compared to cycling. Several variables exhibited non-significant but large effect sizes when comparing the effects of fatigue and fatigue protocol. In conclusion, fatigue alters landing performance and different fatigue protocols result in different performance changes. PMID:20006522

  5. Serotonin and Synaptic Transmission at Invertebrate Neuromuscular Junctions

    PubMed Central

    Wu, Wen-Hui

    2012-01-01

    The serotonergic system in vertebrates and invertebrates has been a focus for over 50 years and will likely continue in the future. Recently, genomic analysis and discovery of alternative splicing and differential expression in tissues have increased the knowledge of serotonin (5-HT) receptor types. Comparative studies can provide useful insights to the wide variety of mechanistic actions of 5-HT responsible for behaviors regulated or modified by 5-HT. To determine cellular responses and influences on neural systems as well as the efferent control of behaviors by the motor units, preparations amenable to detailed studies of synapses are beneficial as working models. The invertebrate neuromuscular junctions (NMJs) offer some unique advantages for such investigations; action of 5-HT at crustacean NMJs has been widely studied, and leech and Aplysia continue to be key organisms. However, there are few studies in insects likely due to the focus in modulation within the CNS and lack of evidence of substantial action of 5-HT at the Drosophila NMJs. There are only a few reports in gastropods and annelids as well as other invertebrates. In this review we highlight some of the key findings of 5-HT actions and receptor types associated at NMJs in a variety of invertebrate preparations in hopes that future studies will build on this knowledge base. PMID:23055788

  6. Frontotemporal dementia: a bridge between dementia and neuromuscular disease

    PubMed Central

    Ng, Adeline SL; Rademakers, Rosa; Miller, BL

    2015-01-01

    The concept that frontotemporal dementia (FTD) is a purely “cortical” dementia has largely been refuted by the recognition of its close association with motor neuron disease, and the identification of transactive response DNA-binding protein 43 (TDP-43) as a major pathological substrate underlying both diseases. Genetic findings have transformed this field and revealed connections between disorders that were previous thought clinically unrelated. The discovery of the C9ORF72 locus as responsible for majority of hereditary FTD, ALS and FTD-ALS cases and the understanding that repeat-containing RNA plays a crucial role in pathogenesis of both disorders has paved the way for development of potential biomarkers and therapeutic targets for these devastating diseases. In this review, we summarize the historical aspects leading up to our current understanding of the genetic, clinical and neuropathological overlap between FTD and ALS, and include brief discussions on chronic traumatic encephalopathy (CTE) given its association with TDP-43 pathology, increased dementia risk and reports of ALS in CTE patients. Additionally we describe other genetic associations between dementia and neuromuscular disease, such as inclusion body myositis with Paget’s disease and frontotemporal dementia (IBMPFD). PMID:25557955

  7. Improving translational studies: lessons from rare neuromuscular diseases

    PubMed Central

    Wells, Dominic

    2015-01-01

    ABSTRACT Animal models play a key role in the development of novel treatments for human disease. This is particularly true for rare diseases – defined as disorders that affect less than 1 in 2000 people in the human population – for which, very often, there are no effective methods of treatment. Pharmaceutical companies are increasingly focussing on the development of therapies for the more than 7000 rare diseases. Because the majority of these are the result of single gene disorders, the exceptional ability to manipulate the mouse genome means that many such studies will take place in the laboratory mouse. But how good are the mouse models and how useful are they in assessing the potential for translational medicine? In this Editorial, I will discuss current difficulties in translational research as well as examples of good laboratory practice and guidelines that are being implemented to improve the translational potential of animal studies in the field of neuromuscular rare diseases. This could represent a potentially useful approach for adoption by other disease fields to achieve a greater success rate in translational studies. PMID:26438690

  8. [Cellular therapy and gene therapy: perspectives in neuromuscular pathology].

    PubMed

    Fardeau, M

    1993-10-01

    Identification of the gene coding for the protein (dystrophin) which is lacking or abnormal in Duchenne or Becker type human muscular dystrophies was a decisive turning point in neuro-muscular pathology. Since that time, a considerable number of gene abnormalities have been identified or at least localized. The severity of these diseases, their steady evolution and the absence of any efficient drug therapy, have lead to the development of new therapeutic approaches based on restoring the genetic capacities of the muscle cell. There are two possibilities for therapy. The first is based on the transfer of myogenic cells derived from the 'satellite' cells normally present at the periphery of muscle fibers. The results obtained from a murine model of Duchenne dystrophy ('mdx' mouse) were very promising. However, the results from application of the same techniques to the canine model (GRMDX) or to affected children are, at the present time, disappointing. A number of biological questions remain to be solved before this technique can be more extensively applied to humans. The second possibility is based on gene transfer, through a viral vector. The adenovirus is presently a possible vector. The first experimental results, on 'mdx' mice, are again very encouraging. Extension of these studies to the canine model is a necessary prerequisite for any human application. It should be noted that these two approaches are complementary. Their future applications may depend on the diffuse or selective nature of the skeletal muscle atrophy, and on whether cardiac and respiratory muscles are involved. PMID:8290312

  9. Degeneration of neuromuscular junction in age and dystrophy.

    PubMed

    Rudolf, Rüdiger; Khan, Muzamil Majid; Labeit, Siegfried; Deschenes, Michael R

    2014-01-01

    Functional denervation is a hallmark of aging sarcopenia as well as of muscular dystrophy. It is thought to be a major factor reducing skeletal muscle mass, particularly in the case of sarcopenia. Neuromuscular junctions (NMJs) serve as the interface between the nervous and skeletal muscular systems, and thus they may receive pathophysiological input of both pre- and post-synaptic origin. Consequently, NMJs are good indicators of motor health on a systemic level. Indeed, upon sarcopenia and dystrophy, NMJs morphologically deteriorate and exhibit altered characteristics of primary signaling molecules, such as nicotinic acetylcholine receptor and agrin. Since a remarkable reversibility of these changes can be observed by exercise, there is significant interest in understanding the molecular mechanisms underlying synaptic deterioration upon aging and dystrophy and how synapses are reset by the aforementioned treatments. Here, we review the literature that describes the phenomena observed at the NMJ in sarcopenic and dystrophic muscle as well as to how these alterations can be reversed and to what extent. In a second part, the current information about molecular machineries underlying these processes is reported. PMID:24904412

  10. Active zones of mammalian neuromuscular junctions: formation, density, and aging

    PubMed Central

    Nishimune, Hiroshi

    2012-01-01

    Presynaptic active zones are synaptic vesicle release sites that playessential roles in the function and pathology of mammalian neuromuscular junctions (NMJs). The molecular mechanisms of active zone organization utilize presynaptic voltage-dependent calcium channels (VDCCs) in NMJs as scaffolding proteins. VDCCs interact extracellularly with the muscle-derived synapse organizer, laminin β2, and interact intracellularly with active zone-specific proteins, such as Bassoon, CAST/Erc2/ELKS2alpha, ELKS, Piccolo, and RIMs. These molecular mechanisms are supported by studies in P/Q- and N-type VDCCs double-knockout mice, and they are consistent with the pathological conditions of Lambert-Eaton myasthenic syndrome and Pierson syndrome, which are caused by autoantibodies against VDCCs or by a laminin β2 mutation. During normal postnatal maturation, NMJs maintain the density of active zones, while NMJs triple their size. However, active zones become impaired during aging. Propitiously, muscle exercise ameliorates the active zone impairment in aged NMJs, which suggests the potential for therapeutic strategies. PMID:23252894

  11. Degeneration of Neuromuscular Junction in Age and Dystrophy

    PubMed Central

    Rudolf, Rüdiger; Khan, Muzamil Majid; Labeit, Siegfried; Deschenes, Michael R.

    2014-01-01

    Functional denervation is a hallmark of aging sarcopenia as well as of muscular dystrophy. It is thought to be a major factor reducing skeletal muscle mass, particularly in the case of sarcopenia. Neuromuscular junctions (NMJs) serve as the interface between the nervous and skeletal muscular systems, and thus they may receive pathophysiological input of both pre- and post-synaptic origin. Consequently, NMJs are good indicators of motor health on a systemic level. Indeed, upon sarcopenia and dystrophy, NMJs morphologically deteriorate and exhibit altered characteristics of primary signaling molecules, such as nicotinic acetylcholine receptor and agrin. Since a remarkable reversibility of these changes can be observed by exercise, there is significant interest in understanding the molecular mechanisms underlying synaptic deterioration upon aging and dystrophy and how synapses are reset by the aforementioned treatments. Here, we review the literature that describes the phenomena observed at the NMJ in sarcopenic and dystrophic muscle as well as to how these alterations can be reversed and to what extent. In a second part, the current information about molecular machineries underlying these processes is reported. PMID:24904412

  12. Molecular Mechanism of Active Zone Organization at Vertebrate Neuromuscular Junctions

    PubMed Central

    Nishimune, Hiroshi

    2013-01-01

    Organization of presynaptic active zones is essential for development, plasticity, and pathology of the nervous system. Recent studies indicate a trans-synaptic molecular mechanism that organizes the active zones by connecting the pre- and the postsynaptic specialization. The presynaptic component of this trans-synaptic mechanism is comprised of cytosolic active zone proteins bound to the cytosolic domains of voltage-dependent calcium channels (P/Q-, N-, and L-type) on the presynaptic membrane. The postsynaptic component of this mechanism is the synapse organizer (laminin β2) that is expressed by the postsynaptic cell and accumulates specifically on top of the postsynaptic specialization. The pre- and the postsynaptic components interact directly between the extracellular domains of calcium channels and laminin β2 to anchor the presynaptic protein complex in front of the postsynaptic specialization. Hence, the presynaptic calcium channel functions as a scaffolding protein for active zone organization and as an ion-conducting channel for synaptic transmission. In contrast to the requirement of calcium influx for synaptic transmission, the formation of the active zone does not require the calcium influx through the calcium channels. Importantly, the active zones of adult synapses are not stable structures and require maintenance for their integrity. Furthermore, aging or diseases of the central and peripheral nervous system impair the active zones. This review will focus on the molecular mechanisms that organize the presynaptic active zones and summarize recent findings at the neuromuscular junctions and other synapses. PMID:22135013

  13. Verifax: Biometric instruments measuring neuromuscular disorders/performance impairments

    NASA Astrophysics Data System (ADS)

    Morgenthaler, George W.; Shrairman, Ruth; Landau, Alexander

    1998-01-01

    VeriFax, founded in 1990 by Dr. Ruth Shrairman and Mr. Alex Landau, began operations with the aim of developing a biometric tool for the verification of signatures from a distance. In the course of developing this VeriFax Autograph technology, two other related applications for the technologies under development at VeriFax became apparent. The first application was in the use of biometric measurements as clinical monitoring tools for physicians investigating neuromuscular diseases (embodied in VeriFax's Neuroskill technology). The second application was to evaluate persons with critical skills (e.g., airline pilots, bus drivers) for physical and mental performance impairments caused by stress, physiological disorders, alcohol, drug abuse, etc. (represented by VeriFax's Impairoscope prototype instrument). This last application raised the possibility of using a space-qualified Impairoscope variant to evaluate astronaut performance with respect to the impacts of stress, fatigue, excessive workload, build-up of toxic chemicals within the space habitat, etc. The three applications of VeriFax's patented technology are accomplished by application-specific modifications of the customized VeriFax software. Strong commercial market potentials exist for all three VeriFax technology applications, and market progress will be presented in more detail below.

  14. Synaptic dynamics at the neuromuscular junction: mechanisms and models.

    PubMed

    Van Essen, D C; Gordon, H; Soha, J M; Fraser, S E

    1990-01-01

    During development, the neuromuscular junction passes through a stage of extensive polyinnervation followed by a period of wholesale synapse elimination. In this report we discuss mechanisms and interactions that could mediate many of the key aspects of these important developmental events. Our emphasis is on (1) establishing an overall conceptual framework within which the role of many distinct cellular interactions and molecular factors can be evaluated, and (2) generating computer simulations that systematically test the adequacy of different models in accounting for a wide range of biological data. Our analysis indicates that several relatively simple mechanisms are each capable of explaining a variety of experimental observations. On the other hand, no one mechanism can account for the full spectrum of experimental results. Thus, it is important to consider models that are based on interactions among multiple mechanisms. A potentially powerful combination is one based on (1) a scaffold within the basal lamina or in the postsynaptic membrane which is induced by nerve terminals and which serves to stabilize terminals by a positive feedback mechanism; (2) a sprouting factor whose release by muscle fibers is down-regulated by activity and perhaps other factors; and (3) an intrinsic tendency of motor neurons to withdraw some connections while allowing others to grow. PMID:2181065

  15. Biomechanical and Neuromuscular Effects of Ankle Taping and Bracing

    PubMed Central

    Wilkerson, Gary B.

    2002-01-01

    Objective: An extensive review of clinically relevant research is provided to assist clinicians in understanding the underlying mechanisms by which various ankle-support systems may provide beneficial effects. Strategies for management of different types of ankle ligament conditions are also discussed. Background: Much of the literature pertaining to ankle instability and external support has focused on assessment of inward displacement of the hindfoot within the frontal plane. Some researchers have emphasized the importance of (1) pathologic rotary displacement of the talus within the transverse plane, (2) the frequent presence of subtalar joint ligament lesions, and (3) the interrelated effects of ankle support on deceleration of inversion velocity and facilitation of neuromuscular response. Description: The traditional method for application of adhesive tape to the ankle primarily restricts inward displacement of the hindfoot within the frontal plane. The biomechanical rationale for a method of ankle taping that restricts lower leg rotation and triplanar displacement of the foot associated with subtalar motion is presented. Clinical Advantages: The lateral subtalar-sling taping procedure may limit strain on the anterior talofibular ligament associated with subtalar inversion, restrain anterolateral rotary subluxation of the talus in the presence of ligament laxity, and protect the subtalar ligaments from excessive loading. The medial subtalar sling may reduce strain on the anterior-inferior tibiofibular syndesmosis and enhance hindfoot-to-forefoot force transfer during the push-off phase of the gait cycle. PMID:12937565

  16. Corrective Neuromuscular Approach to the Treatment of Iliotibial Band Friction Syndrome: A Case Report

    PubMed Central

    Pettitt, Robert; Dolski, Angela

    2000-01-01

    Objective: To describe the evaluation and treatment process for inappropriate functional patterns of neuromuscular activity within the scope of an iliotibial band friction syndrome protocol. Background: Runners with iliotibial band friction syndrome are frequently fitted with orthotic devices to restrict excessive midfoot or rearfoot, or both, motions during the stance phase. These devices may fail to yield favorable results when underlying neuromuscular factors are associated with functional iliotibial band tightening. Differential Diagnosis: Distal biceps femoris tendinitis, popliteal tendinitis, lateral meniscus lesion. Treatment: The athlete's physical examination revealed several patterns of inappropriate neuromuscular activity attributed partly to the prolonged daily wear of beach-type sandals. Modifications of casual footwear and a temporary reduction in training volume were recommended initially to prevent exacerbation of the athlete's condition. Stretching, massage, and soft tissue mobilization were administered in accordance with the athlete's specific needs. The protocol included progressions of nonweightbearing and weightbearing therapeutic exercises. Neuromuscular electric stimulation was incorporated into the protocol to re-educate the role of the first ray within the stance phase of the athlete's walking gait. Uniqueness: Upon stationary examination, this athlete presented with normal lumbar and lower extremity postures. Gait analysis, however, revealed inappropriate dorsiflexion of the great toe during ambulation. Further, the athlete's performances on a series of tests to assess neuromuscular function were substandard. This athlete's response to previous treatment and unique physical findings required a corrective neuromuscular approach that deviates from iliotibial band friction syndrome protocols advocating the use of orthotics. Conclusions: While the role of any single treatment in the athlete's recovery remains unknown, it seems that a

  17. Blocking Delaunay triangulations

    PubMed Central

    Aichholzer, Oswin; Fabila-Monroy, Ruy; Hackl, Thomas; van Kreveld, Marc; Pilz, Alexander; Ramos, Pedro; Vogtenhuber, Birgit

    2013-01-01

    Given a set B of n black points in general position, we say that a set of white points W blocks B if in the Delaunay triangulation of B∪W there is no edge connecting two black points. We give the following bounds for the size of the smallest set W blocking B: (i) 3n/2 white points are always sufficient to block a set of n black points, (ii) if B is in convex position, 5n/4 white points are always sufficient to block it, and (iii) at least n−1 white points are always necessary to block a set of n black points. PMID:23483043

  18. Blocking Delaunay triangulations.

    PubMed

    Aichholzer, Oswin; Fabila-Monroy, Ruy; Hackl, Thomas; van Kreveld, Marc; Pilz, Alexander; Ramos, Pedro; Vogtenhuber, Birgit

    2013-02-01

    Given a set B of n black points in general position, we say that a set of white points W blocks B if in the Delaunay triangulation of [Formula: see text] there is no edge connecting two black points. We give the following bounds for the size of the smallest set W blocking B: (i) [Formula: see text] white points are always sufficient to block a set of n black points, (ii) if B is in convex position, [Formula: see text] white points are always sufficient to block it, and (iii) at least [Formula: see text] white points are always necessary to block a set of n black points. PMID:23483043

  19. Deficits in Endogenous Adenosine Formation by Ecto-5′-Nucleotidase/CD73 Impair Neuromuscular Transmission and Immune Competence in Experimental Autoimmune Myasthenia Gravis

    PubMed Central

    Cristina Costa, Ana; Guerra-Gomes, Sónia; Ferreirinha, Fátima; Magalhães-Cardoso, Maria Teresa; Correia-de-Sá, Paulo

    2015-01-01

    AMP dephosphorylation via ecto-5′-nucleotidase/CD73 is the rate limiting step to generate extracellular adenosine (ADO) from released adenine nucleotides. ADO, via A2A receptors (A2ARs), is a potent modulator of neuromuscular and immunological responses. The pivotal role of ecto-5′-nucleotidase/CD73, in controlling extracellular ADO formation, prompted us to investigate its role in a rat model of experimental autoimmune myasthenia gravis (EAMG). Results show that CD4+CD25+FoxP3+ regulatory T cells express lower amounts of ecto-5′-nucleotidase/CD73 as compared to controls. Reduction of endogenous ADO formation might explain why proliferation of CD4+ T cells failed upon blocking A2A receptors activation with ZM241385 or adenosine deaminase in EAMG animals. Deficits in ADO also contribute to neuromuscular transmission failure in EAMG rats. Rehabilitation of A2AR-mediated immune suppression and facilitation of transmitter release were observed by incubating the cells with the nucleoside precursor, AMP. These findings, together with the characteristic increase in serum adenosine deaminase activity of MG patients, strengthen our hypothesis that the adenosinergic pathway may be dysfunctional in EAMG. Given that endogenous ADO formation is balanced by ecto-5′-nucleotidase/CD73 activity and that A2ARs exert a dual role to restore use-dependent neurocompetence and immune suppression in myasthenics, we hypothesize that stimulation of the two mechanisms may have therapeutic potential in MG. PMID:25691808

  20. Neutralization of the neuromuscular inhibition of venom and taipoxin from the taipan (Oxyuranus scutellatus) by F(ab')2 and whole IgG antivenoms.

    PubMed

    Herrera, María; de Cássia de O Collaço, Rita; Villalta, Mauren; Segura, Álvaro; Vargas, Mariángela; Wright, Christine E; Paiva, Owen K; Matainaho, Teatulohi; Jensen, Simon D; León, Guillermo; Williams, David J; Rodrigues-Simioni, Léa; Gutiérrez, José María

    2016-01-22

    The neuromuscular junction activity of Oxyuranus scutellatus venom and its presynaptic neurotoxin, taipoxin, and their neutralization by two antivenoms were examined in mouse phrenic nerve-diaphragm preparations. The action of taipoxin was also studied at 21°C. The efficacy of the antivenoms was also assessed in an in vivo mouse model. Both antivenoms were effective in neutralizing the neuromuscular blocking activity in preincubation-type experiments. In experiments involving independent addition of venom and antivenoms, neutralization depended on the time interval between venom addition and antivenom application. When taipoxin was incubated for 5, 10 or 20min at 21°C, and antivenom added and temperature increased to 37°C, neutralization was achieved only when the toxin was incubated for 5 or 10min. The neutralization by the two antivenoms in an in vivo model showed that both whole IgG and F(ab')2 antivenoms were effective in neutralizing lethality. Our findings highlight the very rapid action of taipan venom at the nerve terminal, and the poor capacity of antivenoms to revert neurotoxicity as the time interval between venom or taipoxin application and antivenom addition increased. Additionally the disparity between molecular masses of the active substances of the two antivenoms did not result in differences in neutralization. PMID:26621539

  1. Block LU factorization

    NASA Technical Reports Server (NTRS)

    Demmel, James W.; Higham, Nicholas J.; Schreiber, Robert S.

    1992-01-01

    Many of the currently popular 'block algorithms' are scalar algorithms in which the operations have been grouped and reordered into matrix operations. One genuine block algorithm in practical use is block LU factorization, and this has recently been shown by Demmel and Higham to be unstable in general. It is shown here that block LU factorization is stable if A is block diagonally dominant by columns. Moreover, for a general matrix the level of instability in block LU factorization can be founded in terms of the condition number kappa(A) and the growth factor for Gaussian elimination without pivoting. A consequence is that block LU factorization is stable for a matrix A that is symmetric positive definite or point diagonally dominant by rows or columns as long as A is well-conditioned.

  2. Presynaptic neuromuscular action of a methanolic extract from the venom of Rhinella schneideri toad

    PubMed Central

    2014-01-01

    Background Rhinella schneideri, previously known as Bufo paracnemis, is a common toad in many regions of Brazil. Its venom exerts important cardiovascular effects on humans and other animals. Although this toad venom has been the subject of intense investigations, little is known about its neuromuscular activity. Methods The neurotoxicity of a methanolic extract of R. schneideri venom was tested on mouse phrenic nerve-diaphragm (PND) preparations mounted for conventional twitch tension recording – in response to indirect stimulation – and for electrophysiological measurements. Results Venom extract (50 μg/mL) increased the muscle twitch tension in PND preparations but did not significantly alter the resting membrane potential values. Electrophysiological evaluations showed that the extract (50 μg/mL) significantly augmented the frequency of miniature end-plate potential (from 38 ± 3.5 to 88 ± 15 after 60 minutes; n = 5; p < 0.05) and quantal content (from 128 ± 13 to 272 ± 34 after five minutes; n = 5; p < 0.05). Pretreatment with ouabain (1 μg/mL) for five minutes prevented the increase in quantal content (117 ± 18 and 154 ± 33 after five and 60 minutes, respectively). Conclusion These results indicate that the methanolic extract of R. schneideri venom acts primarily presynaptically to enhance neurotransmitter release in mouse phrenic-diaphragm preparations. PMID:25024696

  3. Blocked randomization with randomly selected block sizes.

    PubMed

    Efird, Jimmy

    2011-01-01

    When planning a randomized clinical trial, careful consideration must be given to how participants are selected for various arms of a study. Selection and accidental bias may occur when participants are not assigned to study groups with equal probability. A simple random allocation scheme is a process by which each participant has equal likelihood of being assigned to treatment versus referent groups. However, by chance an unequal number of individuals may be assigned to each arm of the study and thus decrease the power to detect statistically significant differences between groups. Block randomization is a commonly used technique in clinical trial design to reduce bias and achieve balance in the allocation of participants to treatment arms, especially when the sample size is small. This method increases the probability that each arm will contain an equal number of individuals by sequencing participant assignments by block. Yet still, the allocation process may be predictable, for example, when the investigator is not blind and the block size is fixed. This paper provides an overview of blocked randomization and illustrates how to avoid selection bias by using random block sizes. PMID:21318011

  4. Inducible depletion of adult skeletal muscle stem cells impairs the regeneration of neuromuscular junctions

    PubMed Central

    Liu, Wenxuan; Wei-LaPierre, Lan; Klose, Alanna; Dirksen, Robert T; Chakkalakal, Joe V

    2015-01-01

    Skeletal muscle maintenance depends on motor innervation at neuromuscular junctions (NMJs). Multiple mechanisms contribute to NMJ repair and maintenance; however muscle stem cells (satellite cells, SCs), are deemed to have little impact on these processes. Therefore, the applicability of SC studies to attenuate muscle loss due to NMJ deterioration as observed in neuromuscular diseases and aging is ambiguous. We employed mice with an inducible Cre, and conditionally expressed DTA to deplete or GFP to track SCs. We found SC depletion exacerbated muscle atrophy and type transitions connected to neuromuscular disruption. Also, elevated fibrosis and further declines in force generation were specific to SC depletion and neuromuscular disruption. Fate analysis revealed SC activity near regenerating NMJs. Moreover, SC depletion aggravated deficits in reinnervation and post-synaptic morphology at regenerating NMJs. Therefore, our results propose a mechanism whereby further NMJ and skeletal muscle decline ensues upon SC depletion and neuromuscular disruption. DOI: http://dx.doi.org/10.7554/eLife.09221.001 PMID:26312504

  5. Neuromuscular training and the risk of leg injuries in female floorball players: cluster randomised controlled study

    PubMed Central

    2008-01-01

    Objective To investigate whether a neuromuscular training programme is effective in preventing non-contact leg injuries in female floorball players. Design Cluster randomised controlled study. Setting 28 top level female floorball teams in Finland. Participants 457 players (mean age 24 years)—256 (14 teams) in the intervention group and 201 (14 teams) in the control group—followedup for one league season (six months). Intervention A neuromuscular training programme to enhance players’ motor skills and body control, as well as to activate and prepare their neuromuscular system for sports specific manoeuvres. Main outcome measure Acute non-contact injuries of the legs. Results During the season, 72 acute non-contact leg injuries occurred, 20 in the intervention group and 52 in the control group. The injury incidence per 1000 hours playing and practise in the intervention group was 0.65 (95% confidence interval 0.37 to 1.13) and in the control group was 2.08 (1.58 to 2.72). The risk of non-contact leg injury was 66% lower (adjusted incidence rate ratio 0.34, 95% confidence interval 0.20 to 0.57) in the intervention group. Conclusion A neuromuscular training programme was effective in preventing acute non-contact injuries of the legs in female floorball players. Neuromuscular training can be recommended in the weekly training of these athletes. Trial registration Current Controlled Trials ISRCTN26550281. PMID:18595903

  6. A Dutch guideline for the treatment of scoliosis in neuromuscular disorders

    PubMed Central

    Mullender, MG; Blom, NA; De Kleuver, M; Fock, JM; Hitters, WMGC; Horemans, AMC; Kalkman, CJ; Pruijs, JEH; Timmer, RR; Titarsolej, PJ; Van Haasteren, NC; Jager, MJ Van Tol-de; Van Vught, AJ; Van Royen, BJ

    2008-01-01

    Background Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is considered the primary treatment option for correcting severe scoliosis in neuromuscular disorders. Surgery in this population requires a multidisciplinary approach, careful planning, dedicated surgical procedures, and specialized after care. Methods The guideline is based on scientific evidence and expert opinions. A multidisciplinary working group representing experts from all relevant specialties performed the research. A literature search was conducted to collect scientific evidence in answer to specific questions posed by the working group. Literature was classified according to the level of evidence. Results For most aspects of the treatment scientific evidence is scarce and only low level cohort studies were found. Nevertheless, a high degree of consensus was reached about the management of patients with scoliosis in neuromuscular disorders. This was translated into a set of recommendations, which are now officially accepted as a general guideline in the Netherlands. Conclusion In order to optimize the treatment for scoliosis in neuromuscular disorders a Dutch guideline has been composed. This evidence-based, multidisciplinary guideline addresses conservative treatment, the preoperative, perioperative, and postoperative care of scoliosis in neuromuscular disorders. PMID:18822133

  7. Targeting of the ETS Factor Gabpα Disrupts Neuromuscular Junction Synaptic Function▿ §

    PubMed Central

    O'Leary, Debra A.; Noakes, Peter G.; Lavidis, Nick A.; Kola, Ismail; Hertzog, Paul J.; Ristevski, Sika

    2007-01-01

    The GA-binding protein (GABP) transcription factor has been shown in vitro to regulate the expression of the neuromuscular proteins utrophin, acetylcholine esterase, and acetylcholine receptor subunits δ and ɛ through the N-box promoter motif (5′-CCGGAA-3′), but its in vivo function remains unknown. A single point mutation within the N-box of the gene encoding the acetylcholine receptor ɛ subunit has been identified in several patients suffering from postsynaptic congenital myasthenic syndrome, implicating the GA-binding protein in neuromuscular function and disease. Since conventional gene targeting results in an embryonic-lethal phenotype, we used conditional targeting to investigate the role of GABPα in neuromuscular junction and skeletal muscle development. The diaphragm and soleus muscles from mutant mice display alterations in morphology and distribution of acetylcholine receptor clusters at the neuromuscular junction and neurotransmission properties consistent with reduced receptor function. Furthermore, we confirmed decreased expression of the acetylcholine receptor ɛ subunit and increased expression of the γ subunit in skeletal muscle tissues. Therefore, the GABP transcription factor aids in the structural formation and function of neuromuscular junctions by regulating the expression of postsynaptic genes. PMID:17325042

  8. Neuromuscular scoliosis and pelvic fixation in 2015: Where do we stand?

    PubMed Central

    Anari, Jason B; Spiegel, David A; Baldwin, Keith D

    2015-01-01

    Neuromuscular scoliosis is a challenging problem to treat in a heterogeneous patient population. When the decision is made for surgery the surgeon must select a technique employed to correct the curve and achieve the goals of surgery, namely a straight spine over a level pelvis. Pre-operatively the surgeon must ask if pelvic fixation is worth the extra complications and infection risk it introduces to an already compromised host. Since the advent of posterior spinal fusion the technology used for instrumentation has changed drastically. However, many of the common problems seen with the unit rod decades ago we are still dealing with today with pedicle screw technology. Screw cut out, pseudoarthrosis, non-union, prominent hardware, wound complications, and infection are all possible complications when extending a spinal fusion construct to the pelvis in a neuromuscular scoliosis patient. Additionally, placing pelvic fixation in a neuromuscular patient results in extra blood loss, greater surgical time, more extensive dissection with creation of a deep dead space, and an incision that extends close to the rectum in patients who are commonly incontinent. Balancing the risk of placing pelvic fixation when the benefit, some may argue, is limited in non-ambulating patients is difficult when the literature is so mottled. Despite frequent advancements in technology issues with neuromuscular scoliosis remain the same and in the next 10 years we must do what we can to make safe neuromuscular spine surgery a reality. PMID:26396932

  9. miR-30e Blocks Autophagy and Acts Synergistically with Proanthocyanidin for Inhibition of AVEN and BIRC6 to Increase Apoptosis in Glioblastoma Stem Cells and Glioblastoma SNB19 Cells

    PubMed Central

    Chakrabarti, Mrinmay; Klionsky, Daniel J.; Ray, Swapan K.

    2016-01-01

    Glioblastoma is the most common and malignant brain tumor in humans. It is a heterogeneous tumor harboring glioblastoma stem cells (GSC) and other glioblastoma cells that survive and sustain tumor growth in a hypoxic environment via induction of autophagy and resistance to apoptosis. So, a therapeutic strategy to inhibit autophagy and promote apoptosis could greatly help control growth of glioblastoma. We created hypoxia using sodium sulfite (SS) for induction of substantiated autophagy in human GSC and glioblastoma SNB19 cells. Induction of autophagy was confirmed by acridine orange (AO) staining and significant increase in Beclin-1 in autophagic cells. microRNA database (miRDB) search suggested that miR-30e could suppress the autophagy marker Beclin-1 and also inhibit the caspase activation inhibitors (AVEN and BIRC6). Pro-apoptotic effect of proanthocyanidin (PAC) has not yet been explored in glioblastoma cells. Combination of 50 nM miR-30e and 150 μM PAC acted synergistically for inhibition of viability in both cells. This combination therapy most effectively altered expression of molecules for inhibition of autophagy and induced extrinsic and intrinsic pathways of apoptosis through suppression of AVEN and BIRC6. Collectively, combination of miR-30e and PAC is a promising therapeutic strategy to inhibit autophagy and increase apoptosis in GSC and SNB19 cells. PMID:27388765

  10. Neurotic, neuromuscular and autonomic nervous form of magnesium imbalance.

    PubMed

    Durlach, J; Bac, P; Durlach, V; Bara, M; Guiet-Bara, A

    1997-06-01

    The nervous form of magnesium imbalance represents the best documented experimental and clinical aspects of magnesium disorders. The nervous form of primary magnesium deficit (MD) in the adult appears as the best descriptive model for analysis of the symptomatology, aetiology, physiopathology, diagnosis and therapy of the most frequent form of MD. Nervous hyperexcitability due to chronic MD in the adult results in a non-specific clinical pattern with associated central and peripheral neuromuscular symptoms, analogous to the symptomatology previously described in medical literature as latent tetany, hyperventilation syndrome, spasmophilia, chronic fatigue syndrome, neurocirculatory asthenia and idiopathic Barlow's disease. On encountering this non-specific pattern, the signs of neuromuscular hyperexcitability are of much greater importance. Trousseau's sign is less sensitive than Chvostek's sign, but their sensitivities are increased by hyperventilation (Von Bondsdorff's test). Examination of the precordial area will be conducted in order to search clinical stigmata of mitral valve prolapse (MVP) which is a frequent dyskinesia due to chronic MD (about a quarter to one-third of cases). The electromyogram (EMG) shows one (or several) trains of autorhythmic activities beating for more than 2 min of one of the three tetanic activities (uniplets, multiplets or 'complex tonicoclonic tracings') during one of the three facilitation procedures: tourniquet-induced ischaemia lasting 10 min. post-ischaemia lasting 10 min after the removal of the tourniquet and hyperventilation over 5 min. A repetitive EMG constitutes the principal mark of nervous hyperexcitability (NHE) due to MD. The echocardiogram (ECC) is the best tool for detecting MVP, the 2-dimensional ECC with pulsed Doppler being more accurate than time-motion ECC. The routine ionic investigations comprise five static tests: plasma and erythrocyte magnesium, plasma calcium and daily magnesiuria and calciuria. An

  11. Proprioceptive Neuromuscular Facilitation Techniques in Sports Medicine: A Reassessment

    PubMed Central

    Surburg, Paul R.; Schrader, John W.

    1997-01-01

    Objective: The purpose of this survey was for comparison with a similar 1981 survey to determine if proprioceptive neuromuscular facilitation (PNF) techniques are being implemented in the same manner today. Design and Setting: The survey was made available at the 1993 NATA Clinical Symposium. Subjects: The subjects were 131 athletic trainers representing all major national athletic conferences who attended the 1993 NATA Clinical Symposium and who stated that they used PNF exercise in their practice. Measurements: The survey consisted of 15 questions dealing with academic preparation, years of practice, scope and method of preparation in PNF, application of nine PNF techniques to various joints and regions of the body, and the most successful use of PNF techniques. Results: PNF techniques are most frequently applied during rehabilitation of the knee, shoulder, and hip, similar to 1981 except that the use of these techniques during ankle rehabilitation has increased. In both studies, the most frequently used techniques were contract-relax and hold-relax. Two techniques not surveyed in 1981, contract-relax-contract and hold-relax-contract, are becoming techniques of choice for elbow, wrist, hip, and knee rehabilitation. The use of PNF techniques in the muscle re-education phase of rehabilitation is an application identified in this survey not cited by athletic trainers in the 1981 survey. Conclusions: Proprioceptive and kinesthetic deficits are known to occur after certain types of injuries, and the use of PNF techniques to correct these problems is a natural application A contemporary trend in exercise rehabilitation is multiplanar exercises, which are typified by PNF techniques. PMID:16558430

  12. Nocturnal hypoxaemia and hypercapnia in children with neuromuscular disorders.

    PubMed

    Bersanini, Chiara; Khirani, Sonia; Ramirez, Adriana; Lofaso, Frédéric; Aubertin, Guillaume; Beydon, Nicole; Mayer, Michèle; Maincent, Kim; Boulé, Michèle; Fauroux, Brigitte

    2012-05-01

    The aim of the study was to identify daytime predictors of nocturnal gas exchange anomalies in children with neuromuscular disease (NMD) and normal daytime gas exchange. Lung function tests, respiratory muscle evaluation and nocturnal gas exchange were obtained as part of routine evaluation. We included 52 consecutive children with Duchenne muscular dystrophy (n = 20), spinal muscular atrophy (n = 10) and other NMD (n = 22). 20 patients had nocturnal hypoxaemia, defined as minimal arterial oxygen saturation measured by pulse oximetry (S(p,O(2))) <90% for ≥ 2% of night time, and 22 had nocturnal hypercapnia, defined as maximal transcutaneous carbon dioxide tension (P(tc,CO(2))) >50 mmHg for ≥ 2% of night time. Forced vital capacity and helium functional residual capacity correlated with minimal nocturnal S(p,O(2)) (p = 0.009 and p = 0.01, respectively). Daytime pH correlated negatively with maximal nocturnal P(tc,CO(2)) (p=0.005) and daytime arterial carbon dioxide tension (P(a,CO(2))) correlated with the percentage of time with a P(tc,CO(2)) >50 mmHg (p = 0.02). Sniff nasal inspiratory pressure correlated with minimal nocturnal S(p,O(2)) (p = 0.02). Daytime P(a,CO(2)) was a weak predictor of nocturnal hypercapnia (sensitivity 80%; specificity 57%). Daytime lung function and respiratory muscle parameters correlate poorly with nocturnal hypoxaemia and hypercapnia in children with NMD and normal daytime gas exchange, which necessitates more systematic sleep studies in these children. PMID:22135279

  13. Effects of hindlimb unloading on neuromuscular development of neonatal rats

    NASA Technical Reports Server (NTRS)

    Huckstorf, B. L.; Slocum, G. R.; Bain, J. L.; Reiser, P. M.; Sedlak, F. R.; Wong-Riley, M. T.; Riley, D. A.

    2000-01-01

    We hypothesized that hindlimb suspension unloading of 8-day-old neonatal rats would disrupt the normal development of muscle fiber types and the motor innervation of the antigravity (weightbearing) soleus muscles but not extensor digitorum longus (EDL) muscles. Five rats were suspended 4.5 h and returned 1.5 h to the dam for nursing on a 24 h cycle for 9 days. To control for isolation from the dam, the remaining five littermates were removed on the same schedule but not suspended. Another litter of 10 rats housed in the same room provided a vivarium control. Fibers were typed by myofibrillar ATPase histochemistry and immunostaining for embryonic, slow, fast IIA and fast IIB isomyosins. The percentage of multiple innervation and the complexity of singly-innervated motor terminal endings were assessed in silver/cholinesterase stained sections. Unique to the soleus, unloading accelerated production of fast IIA myosin, delayed expression of slow myosin and retarded increases in standardized muscle weight and fiber size. Loss of multiple innervation was not delayed. However, fewer than normal motor nerve endings achieved complexity. Suspended rats continued unloaded hindlimb movements. These findings suggest that motor neurons resolve multiple innervation through nerve impulse activity, whereas the postsynaptic element (muscle fiber) controls endplate size, which regulates motor terminal arborization. Unexpectedly, in the EDL of unloaded rats, transition from embryonic to fast myosin expression was retarded. Suspension-related foot drop, which stretches and chronically loads EDL, may have prevented fast fiber differentiation. These results demonstrate that neuromuscular development of both weightbearing and non-weightbearing muscles in rats is dependent upon and modulated by hindlimb loading.

  14. Pseudoephedrine and circadian rhythm interaction on neuromuscular performance.

    PubMed

    Pallarés, J G; López-Samanes, Á; Fernández-Elías, V E; Aguado-Jiménez, R; Ortega, J F; Gómez, C; Ventura, R; Segura, J; Mora-Rodríguez, R

    2015-12-01

    This study analyzed the effects of pseudoephedrine (PSE) provided at different time of day on neuromuscular performance, side effects, and violation of the current doping cut-off threshold [World Anti-Doping Agency (WADA)]. Nine resistance-trained males carried out bench press and full squat exercises against four incremental loads (25%, 50%, 75%, and 90% one repetition maximum [1RM]), in a randomized, double-blind, cross-over design. Participants ingested either 180 mg of PSE (supra-therapeutic dose) or placebo in the morning (7:00 h; AM(PLAC) and AM(PSE)) and in the afternoon (17:00 h; PM(PLAC) and PM(PSE)). PSE enhanced muscle contraction velocity against 25% and 50% 1RM loads, only when it was ingested in the mornings, and only in the full squat exercise (4.4-8.7%; P < 0.05). PSE ingestion raised urine and plasma PSE concentrations (P < 0.05) regardless of time of day; however, cathine only increased in the urine samples. PSE ingestion resulted in positive tests occurring in 11% of samples, and it rose some adverse side effects such us tachycardia and heart palpitations. Ingestion of a single dose of 180 mg of PSE results in enhanced lower body muscle contraction velocity against low and moderate loads only in the mornings. These mild performance improvements are accompanied by undesirable side effects and an 11% risk of surpassing the doping threshold. PMID:25515692

  15. Maturation and Sex Differences in Neuromuscular Characteristics of Youth Athletes.

    PubMed

    DiStefano, Lindsay J; Martinez, Jessica C; Crowley, Elizabeth; Matteau, Erin; Kerner, Michael S; Boling, Michelle C; Nguyen, Anh-Dung; Trojian, Thomas H

    2015-09-01

    Understanding how neuromuscular factors that are associated with lower extremity injury risk, such as landing kinematics, muscle strength, and flexibility, change as children mature may enhance age-specific recommendations for injury prevention programs. The purpose of this study was to compare these factors in prepubertal, pubertal, and postpubertal male and female athletes. Subjects were classified on maturation stage (prepubertal: 16 males, 15 females, age: 9 ± 1 years; pubertal: 13 males, 12 females, age: 12 ± 3 years; postpubertal: 30 males, 27 females, age: 16 ± 2 years). Researchers measured lower extremity isometric muscle strength and flexibility and evaluated kinematics and vertical ground reaction forces (VGRFs) during a jump-landing task. Three-dimensional kinematics at initial contact (IC), joint displacements, and peak VGRF were calculated. Separate multivariate analyses of variance were performed to evaluate sex and maturation differences (α ≤ 0.05). Postpubertal females landed with less knee flexion at IC (p = 0.006) and demonstrated lower knee extension strength (p = 0.01) than prepubertal and pubertal females. Postpubertal males landed with less hip adduction displacement (postpubertal males = 12.53 ± 6.15°, prepubertal males = 18.84 ± 7.47°; p = 0.04) and less peak VGRF (postpubertal males = 1.53 ± 0.27% body weight [BW], prepubertal males = 1.99 ± 0.32% BW; p = 0.03) compared with prepubertal males. These findings suggest encouraging sagittal plane absorption and decreasing frontal plane motion at the hip, whereas maintaining quadriceps strength may be important for reducing injury risk in postpubertal athletes. PMID:26313573

  16. Wnt4 Participates in the Formation of Vertebrate Neuromuscular Junction

    PubMed Central

    Strochlic, Laure; Falk, Julien; Goillot, Evelyne; Sigoillot, Séverine; Bourgeois, Francine; Delers, Perrine; Rouvière, Jérôme; Swain, Amanda; Castellani, Valérie; Schaeffer, Laurent; Legay, Claire

    2012-01-01

    Neuromuscular junction (NMJ) formation requires the highly coordinated communication of several reciprocal signaling processes between motoneurons and their muscle targets. Identification of the early, spatially restricted cues in target recognition at the NMJ is still poorly documented, especially in mammals. Wnt signaling is one of the key pathways regulating synaptic connectivity. Here, we report that Wnt4 contributes to the formation of vertebrate NMJ in vivo. Results from a microarray screen and quantitative RT-PCR demonstrate that Wnt4 expression is regulated during muscle cell differentiation in vitro and muscle development in vivo, being highly expressed when the first synaptic contacts are formed and subsequently downregulated. Analysis of the mouse Wnt4−/− NMJ phenotype reveals profound innervation defects including motor axons overgrowing and bypassing AChR aggregates with 30% of AChR clusters being unapposed by nerve terminals. In addition, loss of Wnt4 function results in a 35% decrease of the number of prepatterned AChR clusters while Wnt4 overexpression in cultured myotubes increases the number of AChR clusters demonstrating that Wnt4 directly affects postsynaptic differentiation. In contrast, muscle structure and the localization of several synaptic proteins including acetylcholinesterase, MuSK and rapsyn are not perturbed in the Wnt4 mutant. Finally, we identify MuSK as a Wnt4 receptor. Wnt4 not only interacts with MuSK ectodomain but also mediates MuSK activation. Taken together our data reveal a new role for Wnt4 in mammalian NMJ formation that could be mediated by MuSK, a key receptor in synaptogenesis. PMID:22253844

  17. 77 FR 67386 - Announcement of Funding Awards; Indian Community Development Block Grant Program; Fiscal Year 2012

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-09

    ... URBAN DEVELOPMENT Announcement of Funding Awards; Indian Community Development Block Grant Program... and Urban Development Reform Act of 1989, this announcement notifies the public of funding decisions... Funding Availability (NOFA) for the Indian Community Development Block Grant (ICDBG) Program....

  18. The actions of tubocurarine at the frog neuromuscular junction.

    PubMed Central

    Colquhoun, D; Dreyer, F; Sheridan, R E

    1979-01-01

    1. The action of tubocurarine on voltage-clamped frog muscle end-plates has been re-examined by means (a) equilibrium dose-ratio measurements, (b) current fluctuation measurements and (c) voltage-jump relaxation measurements. 2. The equilibrium measurements can be interpreted as implying that tubocurarine has (a) a competitive blocking action, with a dissociation constant of 0.34 microM, which is not dependent on membrane potential, and (b) an additional voltage-dependent blocking action. 3. In the presence of tubocurarine two kinetic components can be seen. The faster one is similar to, but rather faster than, the normal ion channel closing rate. The other is much slower (1--3 sec), and, in relaxation experiments it is in the opposite direction to the fast relaxation. 4. A number of alternative explanations for the results are discussed. The mechanism that fits them best appears to be a combination of competitive block (or block of shut channels), with a strongly voltage-dependent block of open ion channels by tubocurarine. Estimates of the rate constants for channel blocking (and their voltage dependence) are derived. From these estimates the dissociation constant for the binding of tubocurarine to open channels appears to be roughly 0.12 microM at --70 mV and 0.02 microM at --12 mV. 5. Several potential sources of error in the experiments, and in their interpretation, are discussed. The most serious of these are problems associated with diffusion in the small volume of the synaptic cleft, viz. (a) changes in cleft concentration consequent on changes in binding, and (b) ionophoretic flux of antagonist and agonist into the synaptic cleft. PMID:315462

  19. Modulation of spontaneous transmitter release from the frog neuromuscular junction by interacting intracellular Ca(2+) stores: critical role for nicotinic acid-adenine dinucleotide phosphate (NAADP).

    PubMed Central

    Brailoiu, Eugen; Patel, Sandip; Dun, Nae J

    2003-01-01

    Nicotinic acid-adenine dinucleotide phosphate (NAADP) is a recently described potent intracellular Ca(2+)-mobilizing messenger active in a wide range of diverse cell types. In the present study, we have investigated the interaction of NAADP with other Ca(2+)-mobilizing messengers in the release of transmitter at the frog neuromuscular junction. We show, for the first time, that NAADP enhances neurosecretion in response to inositol 1,4,5-trisphosphate (IP(3)), cADP-ribose (cADPR) and sphingosine 1-phosphate (S1P), but not sphingosylphosphorylcholine. Thapsigargin was without effect on transmitter release in response to NAADP, but blocked the responses to subsequent application of IP(3), cADPR and S1P and their potentiation by NAADP. Asynchronous neurotransmitter release may therefore involve functional coupling of endoplasmic reticulum Ca(2+) stores with distinct Ca(2+) stores targeted by NAADP. PMID:12749764

  20. Protein based Block Copolymers

    PubMed Central

    Rabotyagova, Olena S.; Cebe, Peggy; Kaplan, David L.

    2011-01-01

    Advances in genetic engineering have led to the synthesis of protein-based block copolymers with control of chemistry and molecular weight, resulting in unique physical and biological properties. The benefits from incorporating peptide blocks into copolymer designs arise from the fundamental properties of proteins to adopt ordered conformations and to undergo self-assembly, providing control over structure formation at various length scales when compared to conventional block copolymers. This review covers the synthesis, structure, assembly, properties, and applications of protein-based block copolymers. PMID:21235251

  1. Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease

    PubMed Central

    Khan, Muzamil Majid; Lustrino, Danilo; Silveira, Willian A.; Wild, Franziska; Straka, Tatjana; Issop, Yasmin; O’Connor, Emily; Cox, Dan; Reischl, Markus; Marquardt, Till; Labeit, Dittmar; Labeit, Siegfried; Benoit, Evelyne; Molgó, Jordi; Lochmüller, Hanns; Witzemann, Veit; Kettelhut, Isis C.; Navegantes, Luiz C. C.; Pozzan, Tullio; Rudolf, Rüdiger

    2016-01-01

    The distribution and function of sympathetic innervation in skeletal muscle have largely remained elusive. Here we demonstrate that sympathetic neurons make close contact with neuromuscular junctions and form a network in skeletal muscle that may functionally couple different targets including blood vessels, motor neurons, and muscle fibers. Direct stimulation of sympathetic neurons led to activation of muscle postsynaptic β2-adrenoreceptor (ADRB2), cAMP production, and import of the transcriptional coactivator peroxisome proliferator-activated receptor γ-coactivator 1α (PPARGC1A) into myonuclei. Electrophysiological and morphological deficits of neuromuscular junctions upon sympathectomy and in myasthenic mice were rescued by sympathicomimetic treatment. In conclusion, this study identifies the neuromuscular junction as a target of the sympathetic nervous system and shows that sympathetic input is crucial for synapse maintenance and function. PMID:26733679

  2. The use of in-flight foot pressure as a countermeasure to neuromuscular degradation

    NASA Technical Reports Server (NTRS)

    Layne, C. S.; Mulavara, A. P.; Pruett, C. J.; McDonald, P. V.; Kozlovskaya, I. B.; Bloomberg, J. J.

    1998-01-01

    The purpose of this study was to determine whether applying foot pressure to unrestrained subjects during space flight could enhance the neuromuscular activation associated with rapid arm movements. Four men performed unilateral arm raises while wearing--or not wearing--specially designed boots during a 81- or 115-day space flight. Arm acceleration and surface EMG were obtained from selected lower limb and trunk muscles. Pearson r coefficients were used to evaluate similarity in phasic patterns between the two in-flight conditions. In-flight data also were magnitude normalized to the mean voltage value of the muscle activation waveforms obtained during the no-foot-pressure condition to facilitate comparison of activation amplitude between the two in-flight conditions. Foot pressure enhanced neuromuscular activation and somewhat modified the phasic features of the neuromuscular activation during the arm raises.

  3. Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease.

    PubMed

    Khan, Muzamil Majid; Lustrino, Danilo; Silveira, Willian A; Wild, Franziska; Straka, Tatjana; Issop, Yasmin; O'Connor, Emily; Cox, Dan; Reischl, Markus; Marquardt, Till; Labeit, Dittmar; Labeit, Siegfried; Benoit, Evelyne; Molgó, Jordi; Lochmüller, Hanns; Witzemann, Veit; Kettelhut, Isis C; Navegantes, Luiz C C; Pozzan, Tullio; Rudolf, Rüdiger

    2016-01-19

    The distribution and function of sympathetic innervation in skeletal muscle have largely remained elusive. Here we demonstrate that sympathetic neurons make close contact with neuromuscular junctions and form a network in skeletal muscle that may functionally couple different targets including blood vessels, motor neurons, and muscle fibers. Direct stimulation of sympathetic neurons led to activation of muscle postsynaptic β2-adrenoreceptor (ADRB2), cAMP production, and import of the transcriptional coactivator peroxisome proliferator-activated receptor γ-coactivator 1α (PPARGC1A) into myonuclei. Electrophysiological and morphological deficits of neuromuscular junctions upon sympathectomy and in myasthenic mice were rescued by sympathicomimetic treatment. In conclusion, this study identifies the neuromuscular junction as a target of the sympathetic nervous system and shows that sympathetic input is crucial for synapse maintenance and function. PMID:26733679

  4. Bone mineral density evaluation among patients with neuromuscular scoliosis secondary to cerebral palsy☆

    PubMed Central

    Rezende, Rodrigo; Cardoso, Igor Machado; Leonel, Rayana Bomfim; Perim, Larissa Grobério Lopes; Oliveira, Tarcísio Guimarães Silva; Jacob Júnior, Charbel; Júnior, José Lucas Batista; Lourenço, Rafael Burgomeister

    2014-01-01

    Objective To evaluate bone mineral density among patients with neuromuscular scoliosis secondary to quadriplegic cerebral palsy. Methods This was a descriptive prospective study in which both bone densitometric and anthropometric data were evaluated. The inclusion criteria used were that the patients should present quadriplegic cerebral palsy, be confined to a wheelchair, be between 10 and 20 years of age and present neuromuscular scoliosis. Results We evaluated 31 patients (20 females) with a mean age of 14.2 years. Their mean biceps circumference, calf circumference and body mass index were 19.4 cm, 18.6 cm and 16.9 kg/m2, respectively. The mean standard deviation from bone densitometry was −3.2 (z-score), which characterizes osteoporosis. Conclusion There is high incidence of osteoporosis in patients with neuromuscular scoliosis secondary to quadriplegic cerebral palsy. PMID:26229882

  5. Femoral quadriceps neuromuscular electrical stimulation after total knee arthroplasty: a systematic review

    PubMed Central

    Volpato, Helena Bruna Bettoni; Szego, Paulo; Lenza, Mario; Milan, Silvia Lefone; Talerman, Claudia; Ferretti, Mario

    2016-01-01

    ABSTRACT The purpose of this study was to evaluate the effects of neuromuscular electrical stimulation in patients submitted to total knee arthroplasty. This was a systematic review with no language or publication status restriction. Our search was made in Cochrane Library, MEDLINE, Embase and LILACS. Randomized or quasi-randomized clinical trials evaluating neuromuscular electrical stimulation after total knee arthroplasty were included. Four studies with moderate risk of bias and low statistical power were included, totalizing 376 participants. There was no statistically significant difference in knee function, pain and range of motion during 12 month follow-up. This review concluded that neuromuscular electrical stimulation was less effective than traditional rehabilitation in function, muscular strength and range of motion. However, this technique was useful for quadriceps activation during the first days after surgery. PMID:26537511

  6. Chronic exposure to a 60-Hz electric field: effects on neuromuscular function in the rat

    SciTech Connect

    Jaffe, R.A.; Laszewski, B.L.; Carr, D.B.

    1981-01-01

    Neuromuscular function in adult male rats was studied following 30 days of exposure to a 60-Hz electric field at 100 kV/m (unperturbed field strength). Isometric force transducters were attached to the tendons of the plantaris (predominantly fast twitch), and soleus (predominantly slow twitch) muscles in the urethan-anesthetized rat. Square-wave stimuli were delivered to the distal stump of the transected sciatic nerve. Several measurements were used to characterize neuromuscular function, including twitch characteristics, chronaxie, tetanic and posttetanic potentiation, and fatigue and recovery. The results from three independent series of experiments are reported. Only recovery from fatigue in slow-twitch muscles was consistently and significantly affected (enhanced) by electric-field exposure. This effect does not appear to be mediated by field-induced changes in either neuromuscular transmission, or in the contractile mechanism itself. It is suggested that the effect may be mediated secondary to an effect on mechanisms regulating muscle blood flow or metabolism.

  7. Analgesia, sedation, and neuromuscular blockade during targeted temperature management after cardiac arrest.

    PubMed

    Riker, Richard R; Gagnon, David J; May, Teresa; Seder, David B; Fraser, Gilles L

    2015-12-01

    The approach to sedation, analgesia, and neuromuscular blockade during targeted temperature management (TTM) remains largely unstudied, forcing clinicians to adapt previous research from other patient environments. During TTM, very little data guide drug selection, doses, and specific therapeutic goals. Sedation should be deep enough to prevent awareness during neuromuscular blockade, but titration is complex as metabolism and clearance are delayed for almost all drugs during hypothermia. Deeper sedation is associated with prolonged intensive care unit (ICU) and ventilator therapy, increased delirium and infection, and delayed wakening which can confound early critical neurological assessments, potentially resulting in erroneous prognostication and inappropriate withdrawal of life support. We review the potential therapeutic goals for sedation, analgesia, and neuromuscular blockade during TTM; the adverse events associated with that treatment; data suggesting that TTM and organ dysfunction impair drug metabolism; and controversies and potential benefits of specific monitoring. We also highlight the areas needing better research to guide our therapy. PMID:26670815

  8. 76 FR 25407 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-04

    ... Office of Foreign Assets Control Additional Designations, Foreign Narcotics Kingpin Designation Act... property and interests in property are blocked pursuant to the Foreign Narcotics Kingpin Designation Act... targeting the activities of significant foreign narcotics ] traffickers and their organizations on...

  9. 76 FR 56875 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-14

    ... Office of Foreign Assets Control Additional Designations, Foreign Narcotics Kingpin Designation Act... interests in property have been blocked pursuant to the Foreign Narcotics Kingpin Designation Act (``Kingpin... significant foreign narcotics traffickers and their organizations on a worldwide basis. It provides...

  10. Distribution of calcitonin gene-related peptide in vertebrate neuromuscular junctions: relationship to the acetylcholine receptor.

    PubMed

    Csillik, B; Tajti, L; Kovács, T; Kukla, E; Rakic, P; Knyihár-Csillik, E

    1993-10-01

    Calcitonin gene-related peptide (CGRP), regarded by several authors to be involved in maintenance of the acetylcholine receptor, is present in the motor axons of various striated rat muscles. It is present, however, only in motor endplates of several selected striated muscles, where it is located in presynaptic axon terminals of neuromuscular junctions. No immunoreactivity could be seen within synaptic vesicles themselves. In the non-human primate Macaca fasciculata, neuromuscular junctions, including those in the diaphragm, display an intense CGRP reaction. The structure of the simian motor endplates is more elaborate than that of the rat. Amphibian motor nerve endings, both in tetanic and tonic muscles, display CGRP immunoreactivity. In tetanic muscles the CGRP reaction outlines "terminaisons en placque" (true motor end plates) and weakly reacting "terminaisons en grappe" (grape-like endings) in tonic muscles. On supramaximal stimulation of the motor nerve, CGRP is depleted from the affected neuromuscular junctions. Wallerian degeneration of the motor axon results in complete disappearance of CGRP. In most rat muscles in which motor endplates do not normally exhibit CGRP immunoreactivity, e.g., the diaphragm and buccinator muscles, the pre-terminal motor axons are CGRP-positive. After immobilization of such muscles by local bupivacaine injection to rats under brief chloral hydrate anesthesia, CGRP immunoreactivity of the neuromuscular junctions can be elicited because blockade of neuromuscular transmission results in accumulation of CGRP in the endplates. Even more striking is the appearance of CGRP immunoreactivity in normally non-reactive motor endplates during axon regeneration after an experimentally induced Wallerian degeneration of the motor axons. We conclude that CGRP is a regular, genotypically determined component of neuromuscular junctions, present either in a manifest or in a latent form. The latter can be elicited by various experimental approaches

  11. The Role of Neuromuscular Changes in Aging and Knee Osteoarthritis on Dynamic Postural Control

    PubMed Central

    Takacs, Judit; Carpenter, Mark G.; Garland, S. Jayne; Hunt, Michael A.

    2013-01-01

    Knee osteoarthritis (OA) is a chronic joint condition, with 30% of those over the age of 75 exhibiting severe radiographic disease. Nearly 50% of those with knee OA have experienced a fall in the past year. Falls are a considerable public health concern, with a high risk of serious injury and a significant socioeconomic impact. The ability to defend against a fall relies on adequate dynamic postural control, and alterations in dynamic postural control are seen with normal aging. Neuromuscular changes associated with aging may be responsible for some of these alterations in dynamic postural control. Even greater neuromuscular deficits, which may impact dynamic postural control and the ability to defend against a fall, are seen in people with knee OA. There is little evidence to date on how knee OA affects the ability to respond to and defend against falls and the neuromuscular changes that contribute to balance deficits. As a result, this review will: summarize the key characteristics of postural responses to an external perturbation, highlight the changes in dynamic postural control seen with normal aging, review the neuromuscular changes associated with aging that have known and possible effects on dynamic postural control, and summarize the neuromuscular changes and balance problems in knee OA. Future research to better understand the role of neuromuscular changes in knee OA and their effect on dynamic postural control will be suggested. Such an understanding is critical to the successful creation and implementation of fall prevention and treatment programs, in order to reduce the excessive risk of falling in knee OA. PMID:23696951

  12. The conserved P body component HPat/Pat1 negatively regulates synaptic terminal growth at the larval Drosophila neuromuscular junction.

    PubMed

    Pradhan, Sarala J; Nesler, Katherine R; Rosen, Sarah F; Kato, Yasuko; Nakamura, Akira; Ramaswami, Mani; Barbee, Scott A

    2012-12-15

    The temporal and spatial regulation of protein synthesis plays an important role in the control of neural physiology. In axons and dendrites, translationally repressed mRNAs are actively transported to their destinations in a variety of ribonucleoprotein particles (RNPs). A subset of these neuronal RNPs has been shown to contain proteins associated with mRNA processing bodies (P bodies). P bodies are a class of highly conserved cytoplasmic granules that have been linked to both mRNA decay and translational repression via general and miRNA-mediated pathways. Here, we characterize functions for HPat/Pat1 (also known as Patr-1), a core component of P bodies, at the glutamatergic larval Drosophila neuromuscular junction (NMJ). We show that hpat mutants exhibit a strong synaptic hyperplasia at the NMJ. The synaptic defects observed in hpat mutants are associated with rearrangement of the axonal microtubule cytoskeleton suggesting that HPat negatively regulates presynaptic microtubule-based growth during NMJ development. Consistent with this, overexpression of HPat also blocks the rapid growth of presynaptic boutons induced by spaced depolarization. Finally, we demonstrate that HPat interacts genetically with the catalytic subunit of the deadenylase complex (twin/CCR4) and the miRNA pathway (Argonaute 1) to control bouton formation. We propose that HPat is required to target mRNAs involved in the control of microtubule architecture and synaptic terminal growth for repression, presumably in P bodies, via both general and miRNA-mediated mechanisms. PMID:23097047

  13. The conserved P body component HPat/Pat1 negatively regulates synaptic terminal growth at the larval Drosophila neuromuscular junction

    PubMed Central

    Pradhan, Sarala J.; Nesler, Katherine R.; Rosen, Sarah F.; Kato, Yasuko; Nakamura, Akira; Ramaswami, Mani; Barbee, Scott A.

    2012-01-01

    Summary The temporal and spatial regulation of protein synthesis plays an important role in the control of neural physiology. In axons and dendrites, translationally repressed mRNAs are actively transported to their destinations in a variety of ribonucleoprotein particles (RNPs). A subset of these neuronal RNPs has been shown to contain proteins associated with mRNA processing bodies (P bodies). P bodies are a class of highly conserved cytoplasmic granules that have been linked to both mRNA decay and translational repression via general and miRNA-mediated pathways. Here, we characterize functions for HPat/Pat1 (also known as Patr-1), a core component of P bodies, at the glutamatergic larval Drosophila neuromuscular junction (NMJ). We show that hpat mutants exhibit a strong synaptic hyperplasia at the NMJ. The synaptic defects observed in hpat mutants are associated with rearrangement of the axonal microtubule cytoskeleton suggesting that HPat negatively regulates presynaptic microtubule-based growth during NMJ development. Consistent with this, overexpression of HPat also blocks the rapid growth of presynaptic boutons induced by spaced depolarization. Finally, we demonstrate that HPat interacts genetically with the catalytic subunit of the deadenylase complex (twin/CCR4) and the miRNA pathway (Argonaute 1) to control bouton formation. We propose that HPat is required to target mRNAs involved in the control of microtubule architecture and synaptic terminal growth for repression, presumably in P bodies, via both general and miRNA-mediated mechanisms. PMID:23097047

  14. Neuromuscular interaction is required for neurotrophins-mediated locomotor recovery following treadmill training in rat spinal cord injury

    PubMed Central

    Wu, Qinfeng; Cao, Yana; Dong, Chuanming; Wang, Hongxing; Wang, Qinghua; Tong, Weifeng; Li, Xiangzhe

    2016-01-01

    Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training allowed the retention of hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX-A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery. PMID:27190721

  15. Neuromuscular interaction is required for neurotrophins-mediated locomotor recovery following treadmill training in rat spinal cord injury.

    PubMed

    Wu, Qinfeng; Cao, Yana; Dong, Chuanming; Wang, Hongxing; Wang, Qinghua; Tong, Weifeng; Li, Xiangzhe; Shan, Chunlei; Wang, Tong

    2016-01-01

    Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training allowed the retention of hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX-A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery. PMID:27190721

  16. Protein kinase C isoforms at the neuromuscular junction: localization and specific roles in neurotransmission and development

    PubMed Central

    Lanuza, Maria A; Santafe, Manel M; Garcia, Neus; Besalduch, Núria; Tomàs, Marta; Obis, Teresa; Priego, Mercedes; Nelson, Phillip G; Tomàs, Josep

    2014-01-01

    The protein kinase C family (PKC) regulates a variety of neural functions including neurotransmitter release. The selective activation of a wide range of PKC isoforms in different cells and domains is likely to contribute to the functional diversity of PKC phosphorylating activity. In this review, we describe the isoform localization, phosphorylation function, regulation and signalling of the PKC family at the neuromuscular junction. Data show the involvement of the PKC family in several important functions at the neuromuscular junction and in particular in the maturation of the synapse and the modulation of neurotransmission in the adult. PMID:24102585

  17. High Relief Block Printing.

    ERIC Educational Resources Information Center

    Foster, Michael

    1989-01-01

    Explains a method of block printing using styrofoam shapes to make high relief. Describes the creation of the block design as well as the actual printing process. Uses a range of paper types for printing so children can see the results of using different media. (LS)

  18. Surviving Block Scheduling.

    ERIC Educational Resources Information Center

    Haley, Marjorie

    A discussion of block scheduling for second language instruction looks at the advantages and disadvantages and offers some suggestions for classroom management and course organization. It is argued that block scheduling may offer a potential solution to large classes, insufficient time for labs, too little individualized instruction; few…

  19. Block Scheduling Revisited.

    ERIC Educational Resources Information Center

    Queen, J. Allen

    2000-01-01

    Successful block scheduling depends on provision of initial and ongoing instructional training. Teaching strategies should vary and include cooperative learning, the case method, the socratic seminar, synectics, concept attainment, the inquiry method, and simulations. Recommendations for maximizing block scheduling are outlined. (Contains 52…

  20. Thermally actuated wedge block

    DOEpatents

    Queen, Jr., Charles C.

    1980-01-01

    This invention relates to an automatically-operating wedge block for maintaining intimate structural contact over wide temperature ranges, including cryogenic use. The wedging action depends on the relative thermal expansion of two materials having very different coefficients of thermal expansion. The wedge block expands in thickness when cooled to cryogenic temperatures and contracts in thickness when returned to room temperature.

  1. Neuromuscular Consequences of an Extreme Mountain Ultra-Marathon

    PubMed Central

    Millet, Guillaume Y.; Tomazin, Katja; Verges, Samuel; Vincent, Christopher; Bonnefoy, Régis; Boisson, Renée-Claude; Gergelé, Laurent; Féasson, Léonard; Martin, Vincent

    2011-01-01

    We investigated the physiological consequences of one of the most extreme exercises realized by humans in race conditions: a 166-km mountain ultra-marathon (MUM) with 9500 m of positive and negative elevation change. For this purpose, (i) the fatigue induced by the MUM and (ii) the recovery processes over two weeks were assessed. Evaluation of neuromuscular function (NMF) and blood markers of muscle damage and inflammation were performed before and immediately following (n = 22), and 2, 5, 9 and 16 days after the MUM (n = 11) in experienced ultra-marathon runners. Large maximal voluntary contraction decreases occurred after MUM (−35% [95% CI: −28 to −42%] and −39% [95% CI: −32 to −46%] for KE and PF, respectively), with alteration of maximal voluntary activation, mainly for KE (−19% [95% CI: −7 to −32%]). Significant modifications in markers of muscle damage and inflammation were observed after the MUM as suggested by the large changes in creatine kinase (from 144±94 to 13,633±12,626 UI L−1), myoglobin (from 32±22 to 1,432±1,209 µg L−1), and C-Reactive Protein (from <2.0 to 37.7±26.5 mg L−1). Moderate to large reductions in maximal compound muscle action potential amplitude, high-frequency doublet force, and low frequency fatigue (index of excitation-contraction coupling alteration) were also observed for both muscle groups. Sixteen days after MUM, NMF had returned to initial values, with most of the recovery process occurring within 9 days of the race. These findings suggest that the large alterations in NMF after an ultra-marathon race are multi-factorial, including failure of excitation-contraction coupling, which has never been described after prolonged running. It is also concluded that as early as two weeks after such an extreme running exercise, maximal force capacities have returned to baseline. PMID:21364944

  2. Balancing Acts

    MedlinePlus

    ... Current Issue Past Issues Special Section: Focus on Communication Balancing Acts Past Issues / Fall 2008 Table of ... from the National Institute on Deafness and Other Communication Disorders (NIDCD). It involves simulated trips down the ...

  3. Acting Atoms.

    ERIC Educational Resources Information Center

    Farin, Susan Archie

    1997-01-01

    Describes a fun game in which students act as electrons, protons, and neutrons. This activity is designed to help students develop a concrete understanding of the abstract concept of atomic structure. (DKM)

  4. ACT Test

    MedlinePlus

    ... this page helpful? Also known as: ACT; Activated Coagulation Time Formal name: Activated Clotting Time Related tests: ... in the blood called platelets and proteins called coagulation factors are activated in a sequence of steps ...

  5. Evidence-Based Systematic Review: Effects of Neuromuscular Electrical Stimulation on Swallowing and Neural Activation

    ERIC Educational Resources Information Center

    Clark, Heather; Lazarus, Cathy; Arvedson, Joan; Schooling, Tracy; Frymark, Tobi

    2009-01-01

    Purpose: To systematically review the literature examining the effects of neuromuscular electrical stimulation (NMES) on swallowing and neural activation. The review was conducted as part of a series examining the effects of oral motor exercises (OMEs) on speech, swallowing, and neural activation. Method: A systematic search was conducted to…

  6. Metabolic, cardiorespiratory, and neuromuscular fitness performance in children with cerebral palsy: A comparison with healthy youth.

    PubMed

    García, Claudia Cardona; Alcocer-Gamboa, Alberto; Ruiz, Margarita Pérez; Caballero, Ignacio Martínez; Faigenbaum, Avery D; Esteve-Lanao, Jonathan; Saiz, Beatriz Moral; Lorenzo, Teresa Martín; Lara, Sergio Lerma

    2016-04-01

    The aim of this study was to assess metabolic, cardiorespiratory, and neuromuscular fitness parameters in children with spastic cerebral palsy (CP) and to compare these findings with typically developing children. 40 children with CP (21 males, 19 females; mean age, 11.0±3.3 yr; range, 6.5-17.1 yr; Gross Motor Function Classification System levels 1 or 2) and 40 healthy, age- and sex-matched children completed a test battery that consisted of 8 tests and 28 measures that assessed cardio-respiratory fitness, energy expenditure, anaerobic endurance, muscle strength, agility, stability and flexibility. Children with CP had significantly lower performance (P<0.05) on most cardiorespiratory and metabolic tests than those of healthy children, Differences in neuromuscular measures of muscular strength, speed, agility, anaerobic endurance, and flexibility between groups were most apparent. Grouped differences in cardiorespiratory variables revealed a 25% difference in performance, whereas grouped differences in metabolic and neuromuscular measures were 43% and 60%, respectively. The physical fitness of contemporary children with CP is significantly less than healthy, age-matched children. Significant differences in neuromuscular measures between groups can aid in the identification of specific fitness abilities in need of improvement in this population. PMID:27162775

  7. Reversal of profound neuromuscular blockade with sugammadex in an infant after bronchial foreign body removal.

    PubMed

    Azizoglu, Mustafa; Birbicer, Handan; Memis, Suleyman; Taşkınlar, Hakan

    2016-09-01

    Sugammadex is a selective chemical agent that can reverse neuromuscular blockade induced by vecuronium and rocuronium. The aim of this report is to discuss the effectiveness of sugammadex in the reversal of neuromuscular blockade in children younger than 2 years. A 16-month-old boy, weighing 10 kg, was admitted to the pediatric emergency department due to choking, cyanosis, and severe respiratory distress that occurred while he was eating peanuts. In the emergency department, the patient's condition deteriorated, and he went into respiratory arrest. He was immediately intubated and taken to the operating room. A rigid bronchoscopy was performed under general anesthesia, with administration of intravenous pentothal (5 mg/kg), rocuronium (0.6 mg/kg), and fentanyl (0.5 μg/kg) in the operating room. The foreign body was removed within 6 minutes, and the profound neuromuscular blockade was reversed with a dose of 2 mg/kg sugammadex. He was extubated successfully after obtaining the spontaneous respiratory activity, and adequate breathing was restored. Clinical use of sugammadex in children younger than 2 years is not recommended because of the lack of clinical studies. In this case report, the profound neuromuscular blockade was successfully reversed with a dose of 2 mg/kg sugammadex in a 16-month-old boy. However, more prospective clinical studies are required for the safe use of this agent in children. PMID:27555184

  8. Effect of magnesium sulphate on sugammadex reversal time for neuromuscular blockade: a randomised controlled study.

    PubMed

    Germano Filho, P A; Cavalcanti, I L; Barrucand, L; Verçosa, N

    2015-08-01

    Magnesium potentiates neuromuscular blockade. Sugammadex reverses rocuronium-induced blockade. The aim of this study was to determine the effect of pre-treatment with magnesium sulphate on sugammadex reversal time for neuromuscular blockade. Seventy-three patients were randomly assigned to receive magnesium sulphate (40 mg.kg(-1) ) or saline intravenously. After anaesthetic induction, continuous train-of-four monitoring was performed and rocuronium was administered (0.6 mg.kg(-1) ). When a second twitch appeared, the patients received sugammadex (2 mg.kg(-1) ). The median (IQR [range]) reversal time of moderate neuromuscular blockade to a train-of-four ratio of 0.9 facilitated by sugammadex was 115 (93-177.5 [68-315]) s in the magnesium group and 120 (105-140 [70-298]) s in the saline group (p = 0.79). The median (IQR [range]) clinical duration was 45 (35.5-53 [22-102]) min in the magnesium group and 37 (31-43 [19-73]) min in the saline group (p = 0.031). Pre-treatment with magnesium did not significantly affect sugammadex reversal time of moderate neuromuscular blockade induced by rocuronium. PMID:25829048

  9. Upregulation of PKD1L2 provokes a complex neuromuscular disease in the mouse

    PubMed Central

    Mackenzie, Francesca E.; Romero, Rosario; Williams, Debbie; Gillingwater, Thomas; Hilton, Helen; Dick, Jim; Riddoch-Contreras, Joanna; Wong, Frances; Ireson, Lisa; Powles-Glover, Nicola; Riley, Genna; Underhill, Peter; Hough, Tertius; Arkell, Ruth; Greensmith, Linda; Ribchester, Richard R.; Blanco, Gonzalo

    2009-01-01

    Following a screen for neuromuscular mouse mutants, we identified ostes, a novel N-ethyl N-nitrosourea-induced mouse mutant with muscle atrophy. Genetic and biochemical evidence shows that upregulation of the novel, uncharacterized transient receptor potential polycystic (TRPP) channel PKD1L2 (polycystic kidney disease gene 1-like 2) underlies this disease. Ostes mice suffer from chronic neuromuscular impairments including neuromuscular junction degeneration, polyneuronal innervation and myopathy. Ectopic expression of PKD1L2 in transgenic mice reproduced the ostes myopathic changes and, indeed, caused severe muscle atrophy in Tg(Pkd1l2)/Tg(Pkd1l2) mice. Moreover, double-heterozygous mice (ostes/+, Tg(Pkd1l2)/0) suffer from myopathic changes more profound than each heterozygote, indicating positive correlation between PKD1L2 levels and disease severity. We show that, in vivo, PKD1L2 primarily associates with endogenous fatty acid synthase in normal skeletal muscle, and these proteins co-localize to costameric regions of the muscle fibre. In diseased ostes/ostes muscle, both proteins are upregulated, and ostes/ostes mice show signs of abnormal lipid metabolism. This work shows the first role for a TRPP channel in neuromuscular integrity and disease. PMID:19578180

  10. Neurophysiological Strategies for the Diagnosis of Disorders of the Neuromuscular Junction in Children

    ERIC Educational Resources Information Center

    Pitt, Matthew

    2008-01-01

    The disorders of the neuromuscular junction seen in children, the congenital myasthenic syndromes and autoimmune myasthenia gravis, are very rare. Their clinical symptoms and signs may be variable, most notably in the neonate and infant. They should enter the differential diagnosis of many different clinical presentations, such as "floppy infant"…

  11. Monozygous twins with neuromuscular transmission defects at opposite sides of the motor endplate.

    PubMed

    Punga, A R; Nygren, I; Askmark, H; Stålberg, E V

    2009-03-01

    Disorders affecting the postsynaptic side of the neuromuscular junction include autoimmune myasthenia gravis (MG) as well as some of the congenital myasthenic syndromes (CMS). Lambert-Eaton myasthenic syndrome (LEMS) is an acquired autoimmune neuromuscular disorder in which autoantibodies are directed against the presynaptic calcium channels. Here we describe two monozygous twin brothers: case 1 was diagnosed with an indeterminate form of acquired postsynaptic neuromuscular junction defect at age 32 and case 2 with LEMS at age 47. Case 1 presented clinically with mild generalized myasthenic weakness, neurophysiological examination revealed disturbed neuromuscular transmission along with probable myositis and serum analysis regarding antibodies against the acetylcholine receptor and muscle-specific tyrosine kinase was negative. Case 2 presented with proximal muscle fatigue accompanied by areflexia at rest and antibodies against the P/Q-type voltage-gated calcium channels were present. Neurophysiologically, case 2 had reduced baseline compound motor action potential amplitudes on neurography, decrement on low-frequency repetitive nerve stimulation (RNS) and pathological increment on high frequency RNS. To our knowledge this is the first case report of its kind and adds an intriguing contrast to the more common diagnosis of CMS in monozygous twins. PMID:18684214

  12. A system for studying mechanisms of neuromuscular junction development and maintenance.

    PubMed

    Vilmont, Valérie; Cadot, Bruno; Ouanounou, Gilles; Gomes, Edgar R

    2016-07-01

    The neuromuscular junction (NMJ), a cellular synapse between a motor neuron and a skeletal muscle fiber, enables the translation of chemical cues into physical activity. The development of this special structure has been subject to numerous investigations, but its complexity renders in vivo studies particularly difficult to perform. In vitro modeling of the neuromuscular junction represents a powerful tool to delineate fully the fine tuning of events that lead to subcellular specialization at the pre-synaptic and post-synaptic sites. Here, we describe a novel heterologous co-culture in vitro method using rat spinal cord explants with dorsal root ganglia and murine primary myoblasts to study neuromuscular junctions. This system allows the formation and long-term survival of highly differentiated myofibers, motor neurons, supporting glial cells and functional neuromuscular junctions with post-synaptic specialization. Therefore, fundamental aspects of NMJ formation and maintenance can be studied using the described system, which can be adapted to model multiple NMJ-associated disorders. PMID:27226316

  13. Non-invasive neuromuscular electrical stimulation in patients with central nervous system lesions: an educational review.

    PubMed

    Schuhfried, Othmar; Crevenna, Richard; Fialka-Moser, Veronika; Paternostro-Sluga, Tatjana

    2012-02-01

    The aim of this educational review is to provide an overview of the clinical application of transcutaneous electrical stimulation of the extremities in patients with upper motor neurone lesions. In general two methods of electrical stimulation can be distinguished: (i) therapeutic electrical stimulation, and (ii) functional electrical stimulation. Therapeutic electrical stimulation improves neuromuscular functional condition by strengthening muscles, increasing motor control, reducing spasticity, decreasing pain and increasing range of motion. Transcutaneous electrical stimulation may be used for neuromuscular electrical stimulation inducing repetitive muscle contraction, electromyography-triggered neuromuscular electrical stimulation, position-triggered electrical stimulation and subsensory or sensory transcutaneous electric stimulation. Functional electrical stimulation provokes muscle contraction and thereby produces a functionally useful movement during stimulation. In patients with spinal cord injuries or stroke, electrical upper limb neuroprostheses are applied to enhance upper limb and hand function, and electrical lower limb neuroprostheses are applied for restoration of standing and walking. For example, a dropped foot stimulator is used to trigger ankle dorsiflexion to restore gait function. A review of the literature and clinical experience of the use of therapeutic electrical stimulation as well as of functional electrical stimulation in combination with botulinum toxin, exercise therapy and/or splinting are presented. Although the evidence is limited we conclude that neuromuscular electrical stimulation in patients with central nervous system lesions can be an effective modality to improve function, and that combination with other treatments has an additive therapeutic effect. PMID:22334346

  14. Genetic deletion of trkB.T1 increases neuromuscular function

    PubMed Central

    Dorsey, Susan G.; Lovering, Richard M.; Renn, Cynthia L.; Leitch, Carmen C.; Liu, Xinyue; Tallon, Luke J.; Sadzewicz, Lisa DeShong; Pratap, Abhishek; Ott, Sandra; Sengamalay, Naomi; Jones, Kristie M.; Barrick, Colleen; Fulgenzi, Gianluca; Becker, Jodi; Voelker, Kevin; Talmadge, Robert; Harvey, Brandon K.; Wyatt, Ryan M.; Vernon-Pitts, Elizabeth; Zhang, Chao; Shokat, Kevan; Fraser-Liggett, Claire; Balice-Gordon, Rita J.; Tessarollo, Lino

    2012-01-01

    Neurotrophin-dependent activation of the tyrosine kinase receptor trkB.FL modulates neuromuscular synapse maintenance and function; however, it is unclear what role the alternative splice variant, truncated trkB (trkB.T1), may have in the peripheral neuromuscular axis. We examined this question in trkB.T1 null mice and demonstrate that in vivo neuromuscular performance and nerve-evoked muscle tension are significantly increased. In vitro assays indicated that the gain-in-function in trkB.T1−/− animals resulted specifically from an increased muscle contractility, and increased electrically evoked calcium release. In the trkB.T1 null muscle, we identified an increase in Akt activation in resting muscle as well as a significant increase in trkB.FL and Akt activation in response to contractile activity. On the basis of these findings, we conclude that the trkB signaling pathway might represent a novel target for intervention across diseases characterized by deficits in neuromuscular function. PMID:21865582

  15. Current Methodological Issues in the Study of Children with Inherited Neuromuscular Disorders

    ERIC Educational Resources Information Center

    Mercuri, Eugenio; Messina, Sonia; Pane, Marika; Bertini, Enrico

    2008-01-01

    Several clinical trials assessing children with hereditary neuromuscular disorders have been performed over the last decade. These studies highlighted issues related to design and performance of clinical studies assessing children with this group of disorders. This article reviews recent literature and clinical experience in this area,…

  16. Considerations for Feeding Children Who Have a Neuromuscular Disorder. TIES: Therapy in Educational Settings.

    ERIC Educational Resources Information Center

    Hall, Sandra; And Others

    The material in this manual was selected to help non-therapists carry out feeding activities with children who have a neuromuscular disorder such as cerebral palsy. The manual attempts to develop the following competencies: selecting foods of an appropriate consistency, ensuring that the child is positioned correctly for feeding, feeding a child…

  17. Influence of temperature upon effects of crotoxin and gamma-irradiated crotoxin at rat neuromuscular transmission.

    PubMed

    Gallacci, M; Nascimento, N; Rogero, J R; Vassilieff, V S

    2000-04-01

    The influence of temperature upon the effects of crotoxin (CTX), from Crotalus durissus terrificus venom, and gamma-irradiated (60Co, 2000 Gy) crotoxin (iCTX) was studied in rat neuromuscular transmission 'in vitro'. Indirect twitches were evoked in the phrenic-diaphragm preparation by supramaximal strength pulses with a duration of 0.5 ms and frequency of 0.5 Hz. The phospholipase A(2) (PLA(2)) enzymatic activity of CTX and iCTX was assayed against phosphadityl choline in Triton X-100. At 27 degrees C, CTX (14 microg/ml) did not affect the amplitude of indirectly evoked twitches. However, at 37 degrees C, CTX induced a time-dependent blockade of the neuromuscular transmission that started at 90 min and was completed within 240 min. iCTX (14 microg/ml) was inneffective on the neuromuscular transmission either at 27 or 37 degrees C. The PLA(2) enzymatic activity of CTX at 37 degrees C was 84 and that at 27 degrees C was 27 micromol fatty acid released/min/mg protein, and that of the iCTX at 37 degrees C was 39 micromol fatty acid released/min/mg protein. Thus, it was concluded that the mechanism of detoxification of CTX by gamma radiation at the neuromuscular level relies on the loss of its PLA(2) enzymatic activity. PMID:10713471

  18. A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia

    PubMed Central

    Pannérec, Alice; Ireland, Alex; Piasecki, Mathew; Karaz, Sonia; Jacot, Guillaume; Métairon, Sylviane; Danenberg, Esther; Raymond, Frédéric; Descombes, Patrick; McPhee, Jamie S.; Feige, Jerome N.

    2016-01-01

    Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process. PMID:27019136

  19. A system for studying mechanisms of neuromuscular junction development and maintenance

    PubMed Central

    Vilmont, Valérie; Ouanounou, Gilles

    2016-01-01

    The neuromuscular junction (NMJ), a cellular synapse between a motor neuron and a skeletal muscle fiber, enables the translation of chemical cues into physical activity. The development of this special structure has been subject to numerous investigations, but its complexity renders in vivo studies particularly difficult to perform. In vitro modeling of the neuromuscular junction represents a powerful tool to delineate fully the fine tuning of events that lead to subcellular specialization at the pre-synaptic and post-synaptic sites. Here, we describe a novel heterologous co-culture in vitro method using rat spinal cord explants with dorsal root ganglia and murine primary myoblasts to study neuromuscular junctions. This system allows the formation and long-term survival of highly differentiated myofibers, motor neurons, supporting glial cells and functional neuromuscular junctions with post-synaptic specialization. Therefore, fundamental aspects of NMJ formation and maintenance can be studied using the described system, which can be adapted to model multiple NMJ-associated disorders. PMID:27226316

  20. Mirror Visual Feedback Induces Lower Neuromuscular Activity in Children with Spastic Hemiparetic Cerebral Palsy

    ERIC Educational Resources Information Center

    Feltham, Max G.; Ledebt, Annick; Deconinck, Frederik J. A.; Savelsbergh, Geert J. P.

    2010-01-01

    The study examined the effects of mirror feedback information on neuromuscular activation during bimanual coordination in eight children with spastic hemiparetic cerebral palsy (SHCP) and a matched control group. The "mirror box" creates a visual illusion, which gives rise to a visual perception of a zero lag, symmetric movement between the two…

  1. Proprioceptive Neuromuscular Facilitation Flexibility Techniques: Acute Effects on Arterial Blood Pressure.

    ERIC Educational Resources Information Center

    Cornelius, William L.; Craft-Hamm, Kelley

    1988-01-01

    The effects of stretching techniques on arterial blood pressure (ABP) were studied in three groups of 20 men each. Each group performed one of three proprioceptive neuromuscular facilitation (PNF) techniques. Results are presented. The study indicates that the benefits of stretching may outweigh the risk of elevated ABP. (JL)

  2. Effects of neuromuscular electrical stimulation on masticatory muscles in elderly stroke patients

    PubMed Central

    Wang, Joong-San; Lee, Ju-Hwan; Kim, Nyeon-Jun

    2015-01-01

    [Purpose] This study aimed to examine the effects of neuromuscular electrical stimulation on masticatory muscle activation in elderly stroke patients. [Subjects and Methods] The subjects included 20 elderly patients diagnosed with stroke and 10 healthy elderly individuals. The neuromuscular electrical stimulation group received stimulation on the masseter muscle in the affected side for 30 min each day, 3 times per week for 8 weeks. In all the subjects, surface electromyography was used to measure activity of the masseter and temporal muscles in both sides under resting and clenching conditions. [Results] In the neuromuscular electrical stimulation group, after the intervention, an increase in the activity of all of the masticatory muscles was observed during clenching, with a significant increase in the activity of the masseter muscle in the affected side. Significant differences between the groups were not observed after the interventions. [Conclusion] The results of this study suggest that application of neuromuscular electrical stimulation effectively improves muscle activity in elderly stroke patients during clenching, and that this technique can be applied particularly for the improvement of the clenching activity of the masseter muscle in the affected side. PMID:26504289

  3. Metabolic, cardiorespiratory, and neuromuscular fitness performance in children with cerebral palsy: A comparison with healthy youth

    PubMed Central

    García, Claudia Cardona; Alcocer-Gamboa, Alberto; Ruiz, Margarita Pérez; Caballero, Ignacio Martínez; Faigenbaum, Avery D.; Esteve-Lanao, Jonathan; Saiz, Beatriz Moral; Lorenzo, Teresa Martín; Lara, Sergio Lerma

    2016-01-01

    The aim of this study was to assess metabolic, cardiorespiratory, and neuromuscular fitness parameters in children with spastic cerebral palsy (CP) and to compare these findings with typically developing children. 40 children with CP (21 males, 19 females; mean age, 11.0±3.3 yr; range, 6.5–17.1 yr; Gross Motor Function Classification System levels 1 or 2) and 40 healthy, age- and sex-matched children completed a test battery that consisted of 8 tests and 28 measures that assessed cardio-respiratory fitness, energy expenditure, anaerobic endurance, muscle strength, agility, stability and flexibility. Children with CP had significantly lower performance (P<0.05) on most cardiorespiratory and metabolic tests than those of healthy children, Differences in neuromuscular measures of muscular strength, speed, agility, anaerobic endurance, and flexibility between groups were most apparent. Grouped differences in cardiorespiratory variables revealed a 25% difference in performance, whereas grouped differences in metabolic and neuromuscular measures were 43% and 60%, respectively. The physical fitness of contemporary children with CP is significantly less than healthy, age-matched children. Significant differences in neuromuscular measures between groups can aid in the identification of specific fitness abilities in need of improvement in this population. PMID:27162775

  4. Man-Machine Interface System for Neuromuscular Training and Evaluation Based on EMG and MMG Signals

    PubMed Central

    de la Rosa, Ramon; Alonso, Alonso; Carrera, Albano; Durán, Ramon; Fernández, Patricia

    2010-01-01

    This paper presents the UVa-NTS (University of Valladolid Neuromuscular Training System), a multifunction and portable Neuromuscular Training System. The UVa-NTS is designed to analyze the voluntary control of severe neuromotor handicapped patients, their interactive response, and their adaptation to neuromuscular interface systems, such as neural prostheses or domotic applications. Thus, it is an excellent tool to evaluate the residual muscle capabilities in the handicapped. The UVa-NTS is composed of a custom signal conditioning front-end and a computer. The front-end electronics is described thoroughly as well as the overall features of the custom software implementation. The software system is composed of a set of graphical training tools and a processing core. The UVa-NTS works with two classes of neuromuscular signals: the classic myoelectric signals (MES) and, as a novelty, the myomechanic signals (MMS). In order to evaluate the performance of the processing core, a complete analysis has been done to classify its efficiency and to check that it fulfils with the real-time constraints. Tests were performed both with healthy and selected impaired subjects. The adaptation was achieved rapidly, applying a predefined protocol for the UVa-NTS set of training tools. Fine voluntary control was demonstrated to be reached with the myoelectric signals. And the UVa-NTS demonstrated to provide a satisfactory voluntary control when applying the myomechanic signals. PMID:22163515

  5. Effects of partial neuromuscular blockade on carotid baroreflex function during exercise in humans.

    PubMed

    Gallagher, K M; Fadel, P J; Strømstad, M; Ide, K; Smith, S A; Querry, R G; Raven, P B; Secher, N H

    2001-06-15

    1. This investigation was designed to determine the contribution of central command to the resetting of the carotid baroreflex during static and dynamic exercise in humans. 2. Thirteen subjects performed 3.5 min of static one-legged exercise (20 % maximal voluntary contraction) and 7 min dynamic cycling (20 % maximal oxygen uptake) under two conditions: control (no intervention) and with partial neuromuscular blockade (to increase central command influence) using Norcuron (curare). Carotid baroreflex function was determined at rest and during steady-state exercise using a rapid neck pressure/neck suction technique. Whole-body Norcuron was repeatedly administered to effectively reduce hand-grip strength by approximately 50 % of control. 3. Partial neuromuscular blockade increased heart rate, mean arterial pressure, perceived exertion, lactate concentration and plasma noradrenaline concentration during both static and dynamic exercise when compared to control (P < 0.05). No effect was seen at rest. Carotid baroreflex resetting was augmented from control static and dynamic exercise by partial neuromuscular blockade without alterations in gain (P < 0.05). In addition, the operating point of the reflex was relocated away from the centring point (i.e. closer to threshold) during exercise by partial neuromuscular blockade (P < 0.05). 4. These findings suggest that central command actively resets the carotid baroreflex during dynamic and static exercise. PMID:11410641

  6. Decreased muscle endurance associated with diabetic neuropathy may be attributed partially to neuromuscular transmission failure.

    PubMed

    Allen, Matti D; Kimpinski, Kurt; Doherty, Timothy J; Rice, Charles L

    2015-04-15

    Diabetic polyneuropathy (DPN) can cause muscle atrophy, weakness, contractile slowing, and neuromuscular transmission instability. Our objective was to assess the response of the impaired neuromuscular system of DPN in humans when stressed with a sustained maximal voluntary contraction (MVC). Baseline MVC and evoked dorsiflexor contractile properties were assessed in DPN patients (n = 10) and controls (n = 10). Surface electromyography was used to record tibialis anterior evoked maximal compound muscle action potentials (CMAPs) and neuromuscular activity during MVCs. Participants performed a sustained isometric dorsiflexion MVC for which task termination was determined by the inability to sustain ≥60% MVC torque. The fatigue protocol was immediately followed by a maximal twitch, with additional maximal twitches and MVCs assessed at 30 s and 2 min postfatigue. DPN patients fatigued ∼21% more quickly than controls (P < 0.05) and featured less relative electromyographic activity during the first one-third of the fatigue protocol compared with controls (P < 0.05). Immediately following fatigue, maximal twitch torque was reduced similarly (∼20%) in both groups, and concurrently CMAPs were reduced (∼12%) in DPN patients, whereas they were unaffected in controls (P > 0.05). Twitch torque and CMAP amplitude recovered to baseline 30 s postfatigue. Additionally, at 30 s postfatigue, both groups had similar (∼10%) reductions in MVC torque relative to baseline, and MVC strength recovered by 2 min postfatigue. We conclude DPN patients possess less endurance than controls, and neuromuscular transmission failure may contribute to this greater fatigability. PMID:25663671

  7. Family Stress with Chronic Childhood Illness: Cystic Fibrosis, Neuromuscular Disease, and Renal Disease.

    ERIC Educational Resources Information Center

    Holroyd, Jean; Guthrie, Donald

    1986-01-01

    Parents of children with neuromuscular disease, cystic fibrosis, and renal disease were compared with parents of control subjects matched by age to the clinical cases. The three clinical groups exhibited different patterns of stressful response, consistent with the nature of their illnesses and the requirements for care imposed on the families.…

  8. Neuromuscular Adaptations to Eccentric Strength Training in Children and Adolescents with Cerebral Palsy

    ERIC Educational Resources Information Center

    Reid, Siobhan; Hamer, Peter; Alderson, Jacqueline; Lloyd, David

    2010-01-01

    Aim: To determine the neuromuscular outcomes of an eccentric strength-training programme for children and adolescents with cerebral palsy (CP). Method: In this randomised, parallel-group trial with waiting control, 14 participants with CP (six males, eight females; mean age 11y, SD 2y range 9-15y), diagnosed with upper-limb spasticity were…

  9. Blockade of ActRIIB signaling triggers muscle fatigability and metabolic myopathy.

    PubMed

    Relizani, Karima; Mouisel, Etienne; Giannesini, Benoit; Hourdé, Christophe; Patel, Ketan; Morales Gonzalez, Susanne; Jülich, Kristina; Vignaud, Alban; Piétri-Rouxel, France; Fortin, Dominique; Garcia, Luis; Blot, Stéphane; Ritvos, Olli; Bendahan, David; Ferry, Arnaud; Ventura-Clapier, Renée; Schuelke, Markus; Amthor, Helge

    2014-08-01

    Myostatin regulates skeletal muscle size via the activin receptor IIB (ActRIIB). However, its effect on muscle energy metabolism and energy-dependent muscle function remains largely unexplored. This question needs to be solved urgently since various therapies for neuromuscular diseases based on blockade of ActRIIB signaling are being developed. Here, we show in mice, that 4-month pharmacological abrogation of ActRIIB signaling by treatment with soluble ActRIIB-Fc triggers extreme muscle fatigability. This is associated with elevated serum lactate levels and a severe metabolic myopathy in the mdx mouse, an animal model of Duchenne muscular dystrophy. Blockade of ActRIIB signaling downregulates porin, a crucial ADP/ATP shuttle between cytosol and mitochondrial matrix leading to a consecutive deficiency of oxidative phosphorylation as measured by in vivo Phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS). Further, ActRIIB blockade reduces muscle capillarization, which further compounds the metabolic stress. We show that ActRIIB regulates key determinants of muscle metabolism, such as Pparβ, Pgc1α, and Pdk4 thereby optimizing different components of muscle energy metabolism. In conclusion, ActRIIB signaling endows skeletal muscle with high oxidative capacity and low fatigability. The severe metabolic side effects following ActRIIB blockade caution against deploying this strategy, at least in isolation, for treatment of neuromuscular disorders. PMID:24861054

  10. Blockade of ActRIIB Signaling Triggers Muscle Fatigability and Metabolic Myopathy

    PubMed Central

    Relizani, Karima; Mouisel, Etienne; Giannesini, Benoit; Hourdé, Christophe; Patel, Ketan; Morales Gonzalez, Susanne; Jülich, Kristina; Vignaud, Alban; Piétri-Rouxel, France; Fortin, Dominique; Garcia, Luis; Blot, Stéphane; Ritvos, Olli; Bendahan, David; Ferry, Arnaud; Ventura-Clapier, Renée; Schuelke, Markus; Amthor, Helge

    2014-01-01

    Myostatin regulates skeletal muscle size via the activin receptor IIB (ActRIIB). However, its effect on muscle energy metabolism and energy-dependent muscle function remains largely unexplored. This question needs to be solved urgently since various therapies for neuromuscular diseases based on blockade of ActRIIB signaling are being developed. Here, we show in mice, that 4-month pharmacological abrogation of ActRIIB signaling by treatment with soluble ActRIIB-Fc triggers extreme muscle fatigability. This is associated with elevated serum lactate levels and a severe metabolic myopathy in the mdx mouse, an animal model of Duchenne muscular dystrophy. Blockade of ActRIIB signaling downregulates porin, a crucial ADP/ATP shuttle between cytosol and mitochondrial matrix leading to a consecutive deficiency of oxidative phosphorylation as measured by in vivo Phophorus Magnetic Resonance Spectroscopy (31P-MRS). Further, ActRIIB blockade reduces muscle capillarization, which further compounds the metabolic stress. We show that ActRIIB regulates key determinants of muscle metabolism, such as Pparβ, Pgc1α, and Pdk4 thereby optimizing different components of muscle energy metabolism. In conclusion, ActRIIB signaling endows skeletal muscle with high oxidative capacity and low fatigability. The severe metabolic side effects following ActRIIB blockade caution against deploying this strategy, at least in isolation, for treatment of neuromuscular disorders. PMID:24861054

  11. Cell block eleven (left) and cell block fifteen, looking from ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Cell block eleven (left) and cell block fifteen, looking from cell block two into the "Death Row" exercise yard - Eastern State Penitentiary, 2125 Fairmount Avenue, Philadelphia, Philadelphia County, PA

  12. View of cell block eight (left), cell block seven, and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of cell block eight (left), cell block seven, and southwest guard tower, looking from cell block eight roof - Eastern State Penitentiary, 2125 Fairmount Avenue, Philadelphia, Philadelphia County, PA

  13. Blocked tear duct

    MedlinePlus

    ... your baby may have an eye infection called conjunctivitis . ... increase the chance of other infections, such as conjunctivitis. ... be prevented. Proper treatment of nasal infections and conjunctivitis may reduce the risk of having a blocked ...

  14. RX for Writer's Block.

    ERIC Educational Resources Information Center

    Tompkins, Gail E.; Camp, Donna J.

    1988-01-01

    Describes four prewriting techniques that elementary and middle grade students can use to gather and organize ideas for writing, and by so doing, cure writer's block. Techniques discussed are: (1) brainstorming; (2) clustering; (3) freewriting; and (4) cubing.

  15. Superalloy Lattice Block Structures

    NASA Technical Reports Server (NTRS)

    Nathal, M. V.; Whittenberger, J. D.; Hebsur, M. G.; Kantzos, P. T.; Krause, D. L.

    2004-01-01

    Initial investigations of investment cast superalloy lattice block suggest that this technology will yield a low cost approach to utilize the high temperature strength and environmental resistance of superalloys in lightweight, damage tolerant structural configurations. Work to date has demonstrated that relatively large superalloy lattice block panels can be successfully investment cast from both IN-718 and Mar-M247. These castings exhibited mechanical properties consistent with the strength of the same superalloys measured from more conventional castings. The lattice block structure also accommodates significant deformation without failure, and is defect tolerant in fatigue. The potential of lattice block structures opens new opportunities for the use of superalloys in future generations of aircraft applications that demand strength and environmental resistance at elevated temperatures along with low weight.

  16. Block copolymer battery separator

    DOEpatents

    Wong, David; Balsara, Nitash Pervez

    2016-04-26

    The invention herein described is the use of a block copolymer/homopolymer blend for creating nanoporous materials for transport applications. Specifically, this is demonstrated by using the block copolymer poly(styrene-block-ethylene-block-styrene) (SES) and blending it with homopolymer polystyrene (PS). After blending the polymers, a film is cast, and the film is submerged in tetrahydrofuran, which removes the PS. This creates a nanoporous polymer film, whereby the holes are lined with PS. Control of morphology of the system is achieved by manipulating the amount of PS added and the relative size of the PS added. The porous nature of these films was demonstrated by measuring the ionic conductivity in a traditional battery electrolyte, 1M LiPF.sub.6 in EC/DEC (1:1 v/v) using AC impedance spectroscopy and comparing these results to commercially available battery separators.

  17. Genetic modifiers of ambulation in the cooperative international Neuromuscular research group Duchenne natural history study

    PubMed Central

    Bello, Luca; Kesari, Akanchha; Gordish-Dressman, Heather; Cnaan, Avital; Morgenroth, Lauren P; Punetha, Jaya; Duong, Tina; Henricson, Erik K; Pegoraro, Elena; McDonald, Craig M; Hoffman, Eric P

    2015-01-01

    Objective We studied the effects of LTBP4 and SPP1 polymorphisms on age at loss of ambulation (LoA) in a multiethnic Duchenne muscular dystrophy (DMD) cohort. Methods We genotyped SPP1 rs28357094 and LTBP4 haplotype in 283 of 340 participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG-DNHS). Median ages at LoA were compared by Kaplan–Meier analysis and log-rank test. We controlled polymorphism analyses for concurrent effects of glucocorticoid corticosteroid (GC) treatment (time-varying Cox regression) and for population stratification (multidimensional scaling of genome-wide markers). Results Hispanic and South Asian participants (n = 18, 41) lost ambulation 2.7 and 2 years earlier than Caucasian subjects (p = 0.003, <0.001). The TG/GG genotype at SPP1 rs28357094 was associated to 1.2-year-earlier median LoA (p = 0.048). This difference was greater (1.9 years, p = 0.038) in GC-treated participants, whereas no difference was observed in untreated subjects. Cox regression confirmed a significant effect of SPP1 genotype in GC-treated participants (hazard ratio = 1.61, p = 0.016). LTBP4 genotype showed a direction of association with age at LoA as previously reported, but it was not statistically significant. After controlling for population stratification, we confirmed a strong effect of LTBP4 genotype in Caucasians (2.4 years, p = 0.024). Median age at LoA with the protective LTBP4 genotype in this cohort was 15.0 years, 16.0 for those who were treated with GC. Interpretation SPP1 rs28357094 acts as a pharmacodynamic biomarker of GC response, and LTBP4 haplotype modifies age at LoA in the CINRG-DNHS cohort. Adjustment for GC treatment and population stratification appears crucial in assessing genetic modifiers in DMD. PMID:25641372

  18. The neuromuscular activity of Micrurus pyrrhocryptus venom and its neutralization by commercial and specific coral snake antivenoms.

    PubMed

    Camargo, Thiago Magalhães; de Roodt, Adolfo Rafael; da Cruz-Höfling, Maria Alice; Rodrigues-Simioni, Léa

    2011-01-01

    The neuromuscular activity ofMicrurus pyrrochryptus venom was studied in chick biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations. The venom (0.5-50μg/ml) caused irreversible, time- and concentration-dependent blockade, with BC being more sensitive than PND (50% blockade with 10μg/ml in 22±;3min and 62±4min, respectively; mean±SEM, n=6; p<0.05). In BC preparations, venom (0.5μg/ml) progressively abolished ACh-induced contractures, whereas contractures to exogenous KCl and muscle twitches in curarized preparations were unaffected. The venom neither altered creatine kinase release (venom: 25.8±1.75IU/l vs control: 24.3±2.2IU/l, n=6, after 120min), nor it caused significant muscle damage (50μg of venom/ml vs control: 3.5±0.8% vs 1.1±0.7% for PND; 4.3±1.5% vs 1.2±0.5% for BC, n=5). The venom had low PLA(2) activity. Neurotoxicity was effectively neutralized by commercial Micrurus antivenom and specific antivenom. These findings indicate that M. pyrrhocryptus venom acts postsynaptically on nicotinic receptors, with no significant myotoxicity. PMID:21858249

  19. Inhibitory system overstimulation plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis

    PubMed Central

    Tuk, Bert

    2016-01-01

    Based upon a thorough review of published clinical observations regarding the inhibitory system, I hypothesize that this system may play a key role in the pathogenesis of a variety of neuromuscular and neurological diseases. Specifically, excitatory overstimulation, which is commonly reported in neuromuscular and neurological diseases, may be a homeostatic response to inhibitory overstimulation. Involvement of the inhibitory system in disease pathogenesis is highly relevant, given that most approaches currently being developed for treating neuromuscular and neurological diseases focus on reducing excitatory activity rather than reducing inhibitory activity. PMID:27547379

  20. Seismicity of the Jalisco Block

    NASA Astrophysics Data System (ADS)

    Nunez-Cornu, F. J.; Rutz, M.; Camarena-Garcia, M.; Trejo-Gomez, E.; Reyes-Davila, G.; Suarez-Plascencia, C.

    2002-12-01

    In April 2002 began to transmit the stations of the first phase of Jalisco Telemetric Network located at the northwest of Jalisco Block and at the area of Volcan de Fuego (Colima Volcano), in June were deployed four additional MarsLite portable stations in the Bahia de Banderas area, and by the end of August one more portable station at Ceboruco Volcano. The data of these stations jointly with the data from RESCO (Colima Telemetric Network) give us the minimum seismic stations coverage to initiate in a systematic and permanent way the study of the seismicity in this very complex tectonic region. A preliminary analysis of seismicity based on the events registered by the networks using a shutter algorithm, confirms several important features proposed by microseismicity studies carried out between 1996 and 1998. A high level of seismicity inside and below of Rivera plate is observed, this fact suggest a very complex stress pattern acting on this plate. Shallow seismicity at south and east of Bahia de Banderas also suggest a complex stress pattern in this region of the Jalisco Block, events at more than 30 km depth are located under the mouth of the bay and in face of it, a feature denominated Banderas Boundary mark the change of the seismic regime at north of this latitude (20.75°N), however some shallow events were located at the region of Nayarit.

  1. Juvenile Accountability Block Grants Program Reauthorization Act of 2013

    THOMAS, 113th Congress

    Rep. Scott, Robert C. "Bobby" [D-VA-3

    2013-06-13

    07/15/2013 Referred to the Subcommittee on Crime, Terrorism, Homeland Security, and Investigations. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  2. [Editorial introduction: from the structure and functions of the neuromuscular junction to the diseases].

    PubMed

    Takamori, Masaharu

    2011-07-01

    The neuromuscular junction has been recognized as a site for autoimmune and genetic disorders. Myasthenia gravis (MG) is mainly caused by postsynaptic nicotinic acetylcholine receptor (AChR) IgG1 antibodies that are directed against α-subunit 67-76 and 125-147 and activate complement. Thymic abnormalities are present in the autoimmune background. A proportion of MG patients without conformation-dependent AChR antibodies assayed by the cell-based method have muscle-specific tyrosine kinase (MuSK) antibodies which are largely IgG4 and partially IgG1. MuSK is activated by Dok-7 and Lrp4 (agrin receptor) and contributes to AChR clustering at the postsynaptic membrane via various kinase cascades in collaboration with Wnt-MuSK/Frizzled-Dishevelled signaling. Rapsyn interacts with MuSK-linked chaperones to stabilize postsynaptic architecture and also contributes to AChR phosphorylation. MG-associated thymomas express antigens that trigger antibody responses which play a part in disease generation and modification. Among these, ryanodine receptor-1 (RyR1; acts on sarcoplasmic Ca2+ release) antibodies cause muscle contractile weakness. Transient receptor potential canonical-3 (TRPC3) antibodies are also detected in thymoma-associated MG patients; they may participate in muscle contractile weakness because TRPC3 acts on RyR1, and may also impair the refill of sarcoplasmic Ca2+ stores since TRPCs contribute to the receptor-operated Ca2+ influx via the phospholipase C (PLC)-diacylglycerol (DAG) pathway in cooperation with the store-operated, STIM1/Orai1-mediated Ca2+ influx and TRPCs-Homerl-IP3R interaction. Lambert-Eaton myasthenic syndrome (LEMS) is caused by reduced ACh quantal release that occurs mainly because of presynaptic P/Q-type voltage-gated Ca2+ channel (VGCC) antibodies. Physicians should be vigilant for LEMS because it may predict an underlying malignancy, particularly small-cell lung carcinoma; SOX-1 antibodies are usually present in these patients and are

  3. Acute effects of a dopamine/norepinephrine reuptake inhibitor on neuromuscular performance following self-paced exercise in cool and hot environments.

    PubMed

    Onus, Katrina; Cannon, Jack; Liberts, Liz; Marino, Frank E

    2016-08-01

    Dopamine/norepinephrine (DA/NE) reuptake inhibitors have been used to manipulate the central mechanisms affecting arousal and motivation during exercise. Eight healthy, physically active males performed 30min fixed-intensity cycling at 50% Wmax followed by 30min of self paced time trial (TT) with each section interspersed with a 30 s maximal sprint at 9, 19 and 29min. The DA/NE re-uptake inhibitor administered was bupropion (BUP) versus a placebo (PLA) in either warm (32°C, BUP32 or PLA32) or moderate (20°C; BUP20, PLA20) ambient conditions. Core and skin temperature, heart rate and perceptual responses, neuromuscular and hormonal measures were assessed at multiple times throughout the trials and post exercise. Time trial performance remained unchanged across conditions (12.7-13.1km) although core temperature was elevated in the fixed intensity section of the trials for BUP32 and BUP20 but continued to rise only in BUP32 during the time trial reaching 38.6°C (P<0.05). NE increased in all conditions from pre-exercise with BUP32 values peaking at the end of TT to 1245.3±203.1pg/mL (P<0.05) compared to the other conditions. Neuromuscular responses were similar among conditions although peak force was significantly reduced from pre (262±31N) to post (202±31N, P<0.05) exercise along with contraction duration (22%, P<0.05) in BUP20. We conclude that DA/NE re-uptake inhibitors influenced thermoregulation in the heat but not exercise performance. DA/NE re-uptake inhibitors are likely to act centrally to override the inhibitory signals for the cessation of exercise with these drugs acting peripherally to reduce the twitch characteristics of skeletal muscle in cooler conditions. PMID:27503717

  4. Impression block with orientator

    NASA Astrophysics Data System (ADS)

    Brilin, V. I.; Ulyanova, O. S.

    2015-02-01

    Tool review, namely the impression block, applied to check the shape and size of the top of fish as well as to determine the appropriate tool for fishing operation was realized. For multiple application and obtaining of the impress depth of 3 cm and more, the standard volumetric impression blocks with fix rods are used. However, the registered impress of fish is not oriented in space and the rods during fishing are in the extended position. This leads to rods deformation and sinking due to accidental impacts of impression block over the borehole irregularity and finally results in faulty detection of the top end of fishing object in hole. The impression blocks with copy rods and fixed magnetic needle allow estimating the object configuration and fix the position of magnetic needle determining the position of the top end of object in hole. However, the magnetic needle fixation is realized in staged and the rods are in extended position during fishing operations as well as it is in standard design. The most efficient tool is the impression block with copy rods which directs the examined object in the borehole during readings of magnetic needles data from azimuth plate and averaging of readings. This significantly increases the accuracy of fishing toll direction. The rods during fishing are located in the body and extended only when they reach the top of fishing object.

  5. Calcium channel subtypes contributing to acetylcholine release from normal, 4-aminopyridine-treated and myasthenic syndrome auto-antibodies-affected neuromuscular junctions

    PubMed Central

    Giovannini, F; Sher, E; Webster, R; Boot, J; Lang, B

    2002-01-01

    Acetylcholine release at the neuromuscular junction relies on rapid, local and transient calcium increase at presynaptic active zones, triggered by the ion influx through voltage-dependent calcium channels (VDCCs) clustered on the presynaptic membrane. Pharmacological investigation of the role of different VDCC subtypes (L-, N-, P/Q- and R-type) in spontaneous and evoked acetylcholine (ACh) release was carried out in adult mouse neuromuscular junctions (NMJs) under normal and pathological conditions. ω-Agatoxin IVA (500 nM), a specific P/Q-type VDCC blocker, abolished end plate potentials (EPPs) in normal NMJs. However, when neurotransmitter release was potentiated by the presence of the K+ channel blocker 4-aminopyridine (4-AP), an ω-agatoxin IVA- and ω-conotoxin MVIIC-resistant component was detected. This resistant component was only partially sensitive to 1 μM ω-conotoxin GVIA (N-type VDCC blocker), but insensitive to any other known VDCC blockers. Spontaneous release was dependent only on P/Q-type VDCC in normal NMJs. However, in the presence of 4-AP, it relied on L-type VDCCs too. ACh release from normal NMJs was compared with that of NMJs of mice passively injected with IgGs obtained from patients with Lambert-Eaton myasthenic syndrome (LEMS), a disorder characterized by a compromised neurotransmitter release. Differently from normal NMJs, in LEMS IgGs-treated NMJs an ω-agatoxin IVA-resistant EPP component was detected, which was only partially blocked by calciseptine (1 μM), a specific L-type VDCC blocker. Altogether, these data demonstrate that multiple VDCC subtypes are present at the mouse NMJ and that a resistant component can be identified under ‘pharmacological' and/or ‘pathological' conditions. PMID:12163346

  6. An Integrated Approach to Change the Outcome Part II: Targeted Neuromuscular Training Techniques to Reduce Identified ACL Injury Risk Factors

    PubMed Central

    Myer, Gregory D.; Ford, Kevin R.; Brent, Jensen L.; Hewett, Timothy E.

    2014-01-01

    Prior reports indicate that female athletes who demonstrate high knee abduction moments (KAMs) during landing are more responsive to neuromuscular training designed to reduce KAM. Identification of female athletes who demonstrate high KAM, which accurately identifies those at risk for noncontact anterior cruciate ligament (ACL) injury, may be ideal for targeted neuromuscular training. Specific neuromuscular training targeted to the underlying biomechanical components that increase KAM may provide the most efficient and effective training strategy to reduce noncontact ACL injury risk. The purpose of the current commentary is to provide an integrative approach to identify and target mechanistic underpinnings to increased ACL injury in female athletes. Specific neuromuscular training techniques will be presented that address individual algorithm components related to high knee load landing patterns. If these integrated techniques are employed on a widespread basis, prevention strategies for noncontact ACL injury among young female athletes may prove both more effective and efficient. PMID:22580980

  7. Age-related fragmentation of the motor endplate is not associated with impaired neuromuscular transmission in the mouse diaphragm

    PubMed Central

    Willadt, Silvia; Nash, Mark; Slater, Clarke R.

    2016-01-01

    As mammals age, their neuromuscular junctions (NMJs) gradually change their form, acquiring an increasingly fragmented appearance consisting of numerous isolated regions of synaptic differentiation. It has been suggested that this remodelling is associated with impairment of neuromuscular transmission, and that this contributes to age-related muscle weakness in mammals, including humans. The underlying hypothesis, that increasing NMJ fragmentation is associated with impaired transmission, has never been directly tested. Here, by comparing the structure and function of individual NMJs, we show that neuromuscular transmission at the most highly fragmented NMJs in the diaphragms of old (26–28 months) mice is, if anything, stronger than in middle-aged (12–14 months) mice. We suggest that NMJ fragmentation per se is not a reliable indicator of impaired neuromuscular transmission. PMID:27094316

  8. Neuromuscular adaptations predict functional disability independently of clinical pain and psychological factors in patients with chronic non-specific low back pain.

    PubMed

    Dubois, Jean-Daniel; Abboud, Jacques; St-Pierre, Charles; Piché, Mathieu; Descarreaux, Martin

    2014-08-01

    Patients with chronic low back pain exhibit characteristics such as clinical pain, psychological symptoms and neuromuscular adaptations. The purpose of this study was to determine the independent contribution of clinical pain, psychological factors and neuromuscular adaptations to disability in patients with chronic low back pain. Clinical pain intensity, pain catastrophizing, fear-avoidance beliefs, anxiety, neuromuscular adaptations to chronic pain and neuromuscular responses to experimental pain were assessed in 52 patients with chronic low back pain. Lumbar muscle electromyographic activity was assessed during a flexion-extension task (flexion relaxation phenomenon) to assess both chronic neuromuscular adaptations and neuromuscular responses to experimental pain during the task. Multiple regressions showed that independent predictors of disability included neuromuscular adaptations to chronic pain (β=0.25, p=0.006, sr(2)=0.06), neuromuscular responses to experimental pain (β=-0.24, p=0.011, sr(2)=0.05), clinical pain intensity (β=0.28, p=0.002, sr(2)=0.08) and psychological factors (β=0.58, p<0.001, sr(2)=0.32). Together, these predictors accounted for 65% of variance in disability (R(2)=0.65 p<0.001). The current investigation revealed that neuromuscular adaptations are independent from clinical pain intensity and psychological factors, and contribute to inter-individual differences in patients' disability. This suggests that disability, in chronic low back pain patients, is determined by a combination of factors, including clinical pain, psychological factors and neuromuscular adaptations. PMID:24837629

  9. Bactericidal block copolymer micelles.

    PubMed

    Vyhnalkova, Renata; Eisenberg, Adi; van de Ven, Theo

    2011-05-12

    Block copolymer micelles with bactericidal properties were designed to deactivate pathogens such as E. coli bacteria. The micelles of PS-b-PAA and PS-b-P4VP block copolymers were loaded with biocides TCMTB or TCN up to 20 or 30 wt.-%, depending on the type of antibacterial agent. Bacteria were exposed to loaded micelles and bacterial deactivation was evaluated. The micelles loaded with TCN are bactericidal; bacteria are killed in less than two minutes of exposure. The most likely interpretation of the data is that the biocide is transferred to the bacteria by repeated micelle/bacteria contacts, and not via the solution. PMID:21275041

  10. Structural characterization and neuromuscular activity of a new Lys49 phospholipase A(2) homologous (Bp-12) isolated from Bothrops pauloensis snake venom.

    PubMed

    Randazzo-Moura, Priscila; Ponce-Soto, L A; Rodrigues-Simioni, Léa; Marangoni, Sérgio

    2008-09-01

    Bp-12 was isolated from Bothrops pauloensis snake venom in only one chromatographic step in reverse phase HPLC on micro-Bondapack C-18. The molecular mass of 13,789.56 Da was determined by mass spectrometry. The amino acids composition showed that Bp-12 presented high content of Lys, Tyr, Gly, Pro, and 14 half-Cys residues, typical of a basic PLA(2). The sequence of Bp-12 contains 122 amino acid residues: SLFELGKMIL QETGKNPAKS LGAFYCYCGW GSQGQPKDAV DRCCYVHKCC YKKITGCNPK KDRYSYSWKD KTLVCGEDNS CLKELCECDK AVAICLRENL NTYNKKYRYF LKPLCKKADA AC, with a pI value of 8.55 and with a high homology with Lys49 PLA(2) from other snake venoms. In mouse phrenic nerve-diaphragm, the time needed for 50% paralysis was: 45 +/- 6 min (1.4 microM) and 16 +/- 6 min (3.6 microM). Bp-12 can induce indirect and directly blocked evoked twitches, even in the preparations in which Ca(2+) is replaced by Sr(2+), being the addition of d-tubocurarine required for direct blocking. These results identify Bp-12 as a new member of the Lys49 PLA(2) family and shows that this toxin might contribute to the effects of the crude venom on the neuromuscular junction. PMID:18769889

  11. A Place for Block Play.

    ERIC Educational Resources Information Center

    Moore, Gary T.

    1997-01-01

    Discusses the importance of block play--including its contributions to perceptual, fine motor, and cognitive development--and components of a good preschool block play area. Recommends unit blocks complemented by stacking blocks, toys, beads, cubes, and Brio wooden toys. Makes recommendations for space, size, locations and connections to other…

  12. Inhibitory neuromuscular transmission mediated by the P2Y1 purinergic receptor in guinea pig small intestine.

    PubMed

    Wang, Guo-Du; Wang, Xi-Yu; Hu, Hong-Zhen; Liu, Sumei; Gao, Na; Fang, Xiucai; Xia, Yun; Wood, Jackie D

    2007-06-01

    ATP is a putative inhibitory neurotransmitter responsible for inhibitory junction potentials (IJPs) at neuromuscular junctions (IJPs) in the intestine. This study tested the hypothesis that the purinergic P2Y(1) receptor subtype mediates the IJPs. IJPs were evoked by focal electrical stimulation in the myenteric plexus and recorded with "sharp" intracellular microelectrodes in the circular muscle coat. Stimulation evoked three categories of IJPs: 1) purely purinergic IJPs, 2) partially purinergic IJPs, and 3) nonpurinergic IJPs. Purely purinergic IJPs were suppressed by the selective P2Y(1) purinergic receptor antagonist MRS2179. Purely purinergic IJPs comprised 26% of the IJPs. Partially purinergic IJPs (72% of the IJPs) consisted of a component that was abolished by MRS2179 and a second unaffected component. The MRS2179-insensitive component was suppressed or abolished by inhibition of formation of nitric oxide by N(omega)-nitro-l-arginine methyl ester (l-NAME) in some, but not all, IJPs. An unidentified neurotransmitter, different from nitric oxide, mediated the second component in these cases. Nonpurinergic IJPs were a small third category (4%) of IJPs that were abolished by l-NAME and unaffected by MRS2179. Exogenous application of ATP evoked IJP-like hyperpolarizing responses, which were blocked by MRS2179. Application of apamin, which suppresses opening of small-conductance Ca(2+)-operated K(+) channels in the muscle, decreased the amplitude of the purinergic IJPs and the amplitude of IJP-like responses to ATP. The results support ATP as a neurotransmitter for IJPs in the intestine and are consistent with the hypothesis that the P2Y(1) purinergic receptor subtype mediates the action of ATP. PMID:17322065

  13. The use of sugammadex for bariatric surgery: analysis of recovery time from neuromuscular blockade and possible economic impact

    PubMed Central

    De Robertis, Edoardo; Zito Marinosci, Geremia; Romano, Giovanni Marco; Piazza, Ornella; Iannuzzi, Michele; Cirillo, Fabrizio; De Simone, Stefania; Servillo, Giuseppe

    2016-01-01

    Background Neuromuscular block (NMB) monitoring and use of reversal agents accelerate the recovery time and improve the workflow in the operating room. We aimed to compare recovery times after sugammadex or neostigmine administration, and estimate the time spent in operating theater and the possible economic impact of a faster recovery, in morbidly obese patients undergoing bariatric surgery. Methods We conducted a retrospective study that analyzed data from records of morbidly obese patients (body mass index >40 kg/m2) undergoing elective laparoscopic bariatric surgery in which sugammadex or neostigmine were used to reverse NMB. Patients were divided in two groups: group 1 (sugammadex group [SUG]) received rocuronium and sugammadex for reversal and group 2 (neostigmine group [NEO]) received either rocuronium or cisatracurium and neostigmine. Data are presented as mean (standard deviation). Results Compared with NEO, SUG group showed shorter times to achieve train-of-four ratio of 0.9 (P<0.05) and an Aldrete score of 10 (P<0.05), a higher cost (€146.7 vs €3.6 [P<0.05]), plus a remarkable less duration of operating theater occupancy (P<0.05). Sugammadex cost accounted for 2.58% of the total cost per surgery, while neostigmine cost accounted for 0.06%. Total time saved in SUG group was 19.4 hours, which could be used to perform 12 extra laparoscopic sleeve gastrectomies. Conclusion Reversal from NMB was significantly faster with sugammadex than with neostigmine. Although sugammadex was substantially more expensive, duration of operating theater occupancy was reduced with potentially workflow increase or personnel reduced cost. PMID:27418846

  14. A study of tetanic and post-tetanic potentiation of miniature end-plate potentials at the frog neuromuscular junction.

    PubMed Central

    Lev-Tov, A; Rahamimoff, R

    1980-01-01

    1. The involvement of calcium sodium, potassium and magnesium in tetanic and post-tetanic potentiation of miniature end-plate potential frequency was examined at the frog neuromuscular junction using conventional electrophysiological techniques. 2. Tetanic potentiation is larger in calcium containing solutions, than in solutions which generate reversed electrochemical gradient for calcium during nerve activity. 3. Tetanic potentiation increases with stimulation frequency and duration, under both inward and reversed electrochemical gradient for calcium conditions. This indicates that factors, other than calcium entry, participate in tetanic potentiation. 4. Addition of the potassium conductance blocking agent, 3-aminopyridine (5 mM), increases tetanic potentiation in calcium containing media, while depressing it under reversed calcium gradient. 5. Electronic depolarization of the nerve terminal in tetrodotoxin-containing Ringer solution, produces tetanic potentiation under inward gradient, but fails to do so under reversed gradient. This indicates that the entry of sodium ions participates in the generation of tetanic potentiation. 6. Addition of magnesium ions suppresses tetanic potentiation in calcium containing solution, but increases tetanic potentiation under reversed gradient. 7. The results are explained by the hypothesis that calcium entry and intracellular calcium translocation participate in the generation of tetanic potentiation. 8. Both the fast and the slow components (augmentation and potentiation respectively) of post-tetanic potentiation increase in duration, with increase in the tetanic stimulation rate. 9. The decay of post-tetanic potentiation increases: when [Ca]o is elevated by ionophoretic application during the decay phase only, when ouabain is present in the medium or when [Mg]o is elevated. These finding suggest that calcium, sodium and possibly magnesium take part in post-tetanic potentiation. PMID:6973021

  15. 2000 CENSUS BLOCK BOUNDARIES

    EPA Science Inventory

    This data set is a polygon shapefile of the boundaries of Census Blocks in New England derived from U.S. Census Bureau 2000 TIGER/Line data. Numerous attributes pertaining to population are included. TIGER, TIGER/Line, and Census TIGER are registered trademarks of the Bureau o...

  16. Confinement of block copolymers

    SciTech Connect

    1995-12-31

    The following were studied: confinement of block copolymers, free surface confinement, effects of substrate interactions, random copolymers at homopolymer interfaces, phase separation in thin film polymer mixtures, buffing of polymer surfaces, and near edge x-ray absorption fine structure spectroscopy.

  17. A Fluid Block Schedule

    ERIC Educational Resources Information Center

    Ubben, Gerald C.

    1976-01-01

    Achieving flexibility without losing student accountability is a challenge that faces every school. With a fluid block schedule, as described here, accountability is maintained without inhibiting flexibility. An additional advantage is that three levels of schedule decision making take some of the pressure off the principal. (Editor)

  18. Ischemic Nerve Block.

    ERIC Educational Resources Information Center

    Williams, Ian D.

    This experiment investigated the capability for movement and muscle spindle function at successive stages during the development of ischemic nerve block (INB) by pressure cuff. Two male subjects were observed under six randomly ordered conditions. The duration of index finger oscillation to exhaustion, paced at 1.2Hz., was observed on separate…

  19. Spice Blocks Melanoma Growth

    ERIC Educational Resources Information Center

    Science Teacher, 2005

    2005-01-01

    Curcumin, the pungent yellow spice found in both turmeric and curry powders, blocks a key biological pathway needed for development of melanoma and other cancers, according to a study that appears in the journal Cancer. Researchers from The University of Texas M. D. Anderson Cancer Center demonstrate how curcumin stops laboratory strains of…

  20. MHCI promotes developmental synapse elimination and aging-related synapse loss at the vertebrate neuromuscular junction.

    PubMed

    Tetruashvily, Mazell M; McDonald, Marin A; Frietze, Karla K; Boulanger, Lisa M

    2016-08-01

    Synapse elimination at the developing neuromuscular junction (NMJ) sculpts motor circuits, and synapse loss at the aging NMJ drives motor impairments that are a major cause of loss of independence in the elderly. Here we provide evidence that at the NMJ, both developmental synapse elimination and aging-related synapse loss are promoted by specific immune proteins, members of the major histocompatibility complex class I (MHCI). MHCI is expressed at the developing NMJ, and three different methods of reducing MHCI function all disrupt synapse elimination during the second postnatal week, leaving some muscle fibers multiply-innervated, despite otherwise outwardly normal synapse formation and maturation. Conversely, overexpressing MHCI modestly accelerates developmental synapse elimination. MHCI levels at the NMJ rise with aging, and reducing MHCI levels ameliorates muscle denervation in aged mice. These findings identify an unexpected role for MHCI in the elimination of neuromuscular synapses during development, and indicate that reducing MHCI levels can preserve youthful innervation of aging muscle. PMID:26802986

  1. The immediate effect of lumbar spine patterns of neuromuscular joint facilitation in young amateur baseball players.

    PubMed

    Huo, Ming; Maruyama, Hitoshi; Kaneko, Takasumi; Naito, Daiki; Koiso, Yuta

    2013-12-01

    [Purpose] The aim of the study was to investigate the changes in baseball pitching velocity, the functional reach test (FR) and the simple reaction times (SRT) in young amateur baseball players after lumbar spine patterns of neuromuscular joint facilitation (NJF) treatment. [Subjects] The subjects were 11 young amateur baseball players. An NJF intervention and a proprioceptive neuromuscular facilitation (PNF) intervention were performed. The interventions were performed one after the other with one week between them. The order of the interventions was completely randomized. [Methods] The baseball pitching velocity, the FR and the SRT were evaluated before and after treatment. [Results] In the NJF group, there were significant differences in baseball pitching velocity, FR and SRT after treatment. In the PNF group, there was a significant difference in SRT after treatment. [Conclusion] NJF intervention shortens the SRT, increases the baseball pitching velocity and FR, and may be recommended to improve performance in baseball players. PMID:24409011

  2. CLINICAL APPROACH TO THE DIAGNOSTIC EVALUATION OF HERDITARY AND ACQUIRED NEUROMUSCULAR DISEASES

    PubMed Central

    McDonald, Craig M.

    2012-01-01

    SYNOPSIS In the context of a neuromuscular disease diagnostic evaluation, the clinician still must be able to obtain a relevant patient and family history and perform focused general, musculoskeletal, neurologic and functional physical examinations to direct further diagnostic evaluations. Laboratory studies for hereditary neuromuscular diseases include relevant molecular genetic studies. The EMG and nerve conduction studies remain an extension of the physical examination and help to guide further diagnostic studies such as molecular genetic studies, and muscle and nerve biopsies. All diagnostic information needs to be interpreted not in isolation, but within the context of relevant historical information, family history, physical examination findings, and laboratory data, electrophysiologic findings, pathologic findings, and molecular genetic findings if obtained. PMID:22938875

  3. Neuromuscular Junctions as Key Contributors and Therapeutic Targets in Spinal Muscular Atrophy

    PubMed Central

    Boido, Marina; Vercelli, Alessandro

    2016-01-01

    Spinal muscular atrophy (SMA) is a recessive autosomal neuromuscular disease, representing the most common fatal pediatric pathology. Even though, classically and in a simplistic way, it is categorized as a motor neuron (MN) disease, there is an increasing general consensus that its pathogenesis is more complex than expected. In particular, neuromuscular junctions (NMJs) are affected by dramatic alterations, including immaturity, denervation and neurofilament accumulation, associated to impaired synaptic functions: these abnormalities may in turn have a detrimental effect on MN survival. Here, we provide a description of NMJ development/maintenance/maturation in physiological conditions and in SMA, focusing on pivotal molecules and on the time-course of pathological events. Moreover, since NMJs could represent an important target to be exploited for counteracting the pathology progression, we also describe several therapeutic strategies that, directly or indirectly, aim at NMJs. PMID:26869891

  4. [Neuromuscular signal transmission in adulthood. Current facets of acquired and hereditary disorders].

    PubMed

    Abicht, A; Kröger, S; Schoser, B

    2011-06-01

    The availability of early diagnosis and modern effective therapies has reduced mortality and disability linked to late-onset acquired or hereditary neuromuscular transmission disorders. Nevertheless, identification of the pathogenesis of these diseases remains a challenge. In addition to non-specific and fluctuating presenting symptoms current diagnostic work-up strategies include electrophysiology, antibody measurements and less frequently molecular genetics. For differential diagnostic purposes there is an increasing demand for improving awareness concerning late-onset congenital myasthenic syndromes (CMS) which are rare but nevertheless symptomatically treatable diseases. Especially in seronegative myasthenic syndromes, molecular genetic analyses of CMS genes should be integrated into the differential diagnostic work-up. Therefore, some facets of neuromuscular synaptogenesis in the context of seronegative acquired myasthenic syndromes and recently uncovered congenital myasthenic syndromes are reviewed. PMID:21584790

  5. Recommendations for anesthesia and perioperative management of patients with neuromuscular disorders.

    PubMed

    Racca, F; Mongini, T; Wolfler, A; Vianello, A; Cutrera, R; Del Sorbo, L; Capello, E C; Gregoretti, C; Massa, R; De Luca, D; Conti, G; Tegazzin, V; Toscano, A; Ranieri, V M

    2013-04-01

    Patients with neuromuscular disorders are at high risk of intraoperative and postoperative complications. General anesthesia in these patients may exacerbate respiratory and cardiovascular failure due to a marked sensitivity to several anesthetic drugs. Moreover, succinylcholine and halogenated agents can trigger life-threatening reactions, such as malignant hyperthermia, rhabdomyolysis and severe hyperkalemia. Therefore, regional anesthesia should be used whenever possible. If general anesthesia is unavoidable, special precautions must be taken. In particular, for patients at increased risk of respiratory complications (i.e., postoperative atelectasis, acute respiratory failure, nosocomial infections), noninvasive ventilation associated with aggressive airway clearance techniques can successfully treat upper airway obstruction, hypoventilation and airway secretion retention, avoiding prolonged intubation and tracheotomy. Anesthesia and perioperative management of patients with neuromuscular disorders are described in this article. To grade the strength of recommendations and the quality of evidence we adopted the GRADE approach. In case of low-quality evidence, these recommendations represent the collective opinion of the expert panel. PMID:23419334

  6. Temperature Sensitivity of the Pyloric Neuromuscular System and Its Modulation by Dopamine

    PubMed Central

    Thuma, Jeffrey B.; Hobbs, Kevin H.; Burstein, Helaine J.; Seiter, Natasha S.; Hooper, Scott L.

    2013-01-01

    We report here the effects of temperature on the p1 neuromuscular system of the stomatogastric system of the lobster (Panulirus interruptus). Muscle force generation, in response to both the spontaneously rhythmic in vitro pyloric network neural activity and direct, controlled motor nerve stimulation, dramatically decreased as temperature increased, sufficiently that stomach movements would very unlikely be maintained at warm temperatures. However, animals fed in warm tanks showed statistically identical food digestion to those in cold tanks. Applying dopamine, a circulating hormone in crustacea, increased muscle force production at all temperatures and abolished neuromuscular system temperature dependence. Modulation may thus exist not only to increase the diversity of produced behaviors, but also to maintain individual behaviors when environmental conditions (such as temperature) vary. PMID:23840789

  7. Enhancement of Neuromuscular Activity by Natural Specimens and Cultured Mycelia of Cordyceps sinensis in Mice.

    PubMed

    Singh, K P; Meena, H S; Negi, P S

    2014-09-01

    The present study was aimed to evaluate the effect of natural specimen and laboratory cultured mycelia of Cordyceps sinensis on neuromuscular activity in mice. The powder of natural specimen and laboratory cultured Cordyceps sinensis was orally administered at the dose rate of 100, 300 and 500 mg/kg for 30 days. Natural specimen and in vitro propagated Cordyceps sinensis showed significant (P<0.05) enhancement in neuromuscular endurance and antidepressant activity at 300 and 500 mg/kg as compared to the control group. However, the fungus did not proved to be as effective as fluoxetine in exhibiting antidepressant action. Muscular endurance was determined on a Rota rod apparatus while antidepressant (mood elevating) activity was measured on a photoactometer in Swiss albino mice. The effects produced by both natural specimens and laboratory cultured Cordyceps sinensis were comparable and showed almost equal potency. PMID:25425763

  8. [What are the effects of the aging of the neuromuscular system on postural stability?].

    PubMed

    Cattagni, Thomas; Scaglioni, Gil; Cornu, Christophe; Berrut, Gilles; Martin, Alain

    2015-12-01

    Aging is frequently associated with a decreased postural stability, essentially after 60 years, leading to an increased risk of falling. In this article we propose to highlight the influence of the aging of the neuromuscular system on postural stability when standing upright. To maintain balance while standing upright, human needs to control the activity of ankle muscles and particularly the plantar flexors. During the aging process, the performance of these muscles are strongly altered. It is commonly observed large deficits in elderly people with history of falls. Some authors reported an inverse correlation between the amplitude of postural sway and the capacity of force production of ankle muscles suggesting that the assessment of neuromuscular function could be an index of postural stability or even of the falling risk. Finally, enhance the strength of ankle muscles in elderly through physical exercise could be an adequate intervention to improve postural stability and reduce the incidence of falls. PMID:26707554

  9. Mixed cholinergic/glutamatergic neuromuscular innervation of Onychophora: a combined histochemical/electrophysiological study.

    PubMed

    Stern, Michael; Bicker, Gerd

    2008-08-01

    Morphological and molecular phylogenetic data show that the Onychophora are close relatives of the Arthropoda. However, onychophoran neuromuscular junctions have been reported to employ acetylcholine, as in annelids, nematodes, and other bilaterians, rather than glutamate, as in arthropods. Here, we show that the large longitudinal muscles of Peripatoides respond indeed only to acetylcholine, whereas the oblique and ring muscles of the body wall are sensitive both to acetylcholine and to L-glutamate. Moreover, cytochemical staining reveals both acetylcholinesterase- and glutamate-positive synaptic boutons on oblique and ring muscles. These novel findings agree with a phylogenetic position of onychophorans basal to that of the arthropods. Although the glutamatergic phenotype of excitatory neuromuscular transmission may be a characteristic feature of arthropods and present even in a subset of onychophoran motor neurons, the motor neurons of the longitudinal muscles still retain the cholinergic phenotype typical for annelids and other taxa. PMID:18563449

  10. Tilted seat position for non-ambulant individuals with neurological and neuromuscular impairment: a systematic review

    PubMed Central

    Porter, D; Pountney, TE

    2008-01-01

    Objective: To determine the effects of tilt-in-space seating on outcomes for people with neurological or neuromuscular impairment who cannot walk. Data sources: Search through electronic databases (MEDLINE, Embase, CINAHL, AMED). Discussions with researchers who are active in field. Review methods: Selection criteria included interventional studies that investigated the effects of seat tilt on outcome or observational studies that identified outcomes for those who had used tilt-in-space seating in populations with neurological or neuromuscular impairments. Two reviewers independently selected trials for inclusion, assessed quality and extracted data. Results: Nineteen studies were identified which fulfilled the selection criteria. Seventeen of these were essentially before–after studies investigating the immediate effects of tilting the seating. All studies looked at populations with neurological impairment, and most were on children with cerebral palsy (n = 8) or adults with spinal cord injury (n = 8). Reviewer's conclusion: Posterior tilt can reduce pressures at the interface under the pelvis. PMID:18042602

  11. [Neuromuscular dynamic scapular winging: Clinical, electromyographic and magnetic resonance imaging diagnosis].

    PubMed

    Nguyen, Christelle; Guérini, Henri; Roren, Alexandra; Zauderer, Jennifer; Vuillemin, Valérie; Seror, Paul; Ouaknine, Michaël; Palazzo, Clémence; Bourdet, Christopher; Pluot, Étienne; Roby-Brami, Agnès; Drapé, Jean-Luc; Rannou, François; Poiraudeau, Serge; Lefèvre-Colau, Marie-Martine

    2015-12-01

    Dyskinesia of the scapula is a clinical diagnosis and includes all disorders affecting scapula positioning and movement whatever its etiology. Scapular winging is a subtype of scapular dyskinesia due to a dynamic prominence of the medial border of the scapula (DSW) secondary to neuromuscular imbalance in the scapulothoracic stabilizer muscles. The two most common causes of DSW are microtraumatic or idiopathic lesions of the long thoracic nerve (that innerves the serratus anterior) or the accessory nerve (that innerves the trapezius). Diagnosis of DSW is clinical and electromyographic. Use of magnetic resonance imaging (MRI) could be of interest to distinguish lesion secondary to a long thoracic nerve from accessory nerve and to rule out scapular dyskinesia related to other shoulder disorders. Causal neuromuscular lesion diagnosis in DSW is challenging. Clinical examinations, combined with scapular MRI, could help to their specific diagnosis, determining their stage, ruling out differential diagnosis and thus give raise to more targeted treatment. PMID:26433832

  12. [Masquerading bundle branch block].

    PubMed

    Kukla, Piotr; Baranchuk, Adrian; Jastrzębski, Marek; Bryniarski, Leszek

    2014-01-01

    We here describe a surface 12-lead electrocardiogram (ECG) of a 72-year-old female with a prior history of breast cancer and chemotherapy-induced cardiomyopathy. An echocardiogram revealed left ventricular dysfunction, ejection fraction of 23%, with mild enlarged left ventricle. The 12-lead ECG showed atrial fibrillation with a mean heart rate of about 100 bpm, QRS duration 160 ms, QT interval 400 ms, right bundle branch block (RBBB) and left anterior fascicular block (LAFB). The combination of RBBB features in the precordial leads and LAFB features in the limb leads is known as ''masquerading bundle branch block''. In most cases of RBBB and LAFB, the QRS axis deviation is located between - 80 to -120 degrees. Rarely, when predominant left ventricular forces are present, the QRS axis deviation is near about -90 degrees, turning the pattern into an atypical form. In a situation of RBBB associated with LAFB, the S wave can be absent or very small in lead I. Such a situation is the result of not only purely LAFB but also with left ventricular hypertrophy and/or focal block due to scar (extensive anterior myocardial infarction) or fibrosis (cardiomyopathy). Sometimes, this specific ECG pattern is mistaken for LBBB. RBBB with LAFB may imitate LBBB either in the limb leads (known as 'standard masquerading' - absence of S wave in lead I), or in the precordial leads (called 'precordial masquerading' - absence of S wave in leads V₅ and V₆). Our ECG showed both these types of masquerading bundle branch block - absence of S wave in lead I and in leads V₅ and V₆. PMID:24469750

  13. Neuromuscular Activity of Upper and Lower Limbs during two Backstroke Swimming Start Variants

    PubMed Central

    De Jesus, Karla; De Jesus, Kelly; Medeiros, Alexandre I. A.; Gonçalves, Pedro; Figueiredo, Pedro; Fernandes, Ricardo J.; Vilas-Boas, João Paulo

    2015-01-01

    swimmers’ vertex reaches the 15 m mark) is decisive in short distance events. In 2008, FINA approved the Omega OSB11 starting block (Swiss Timing Ltd., Switzerland) with two horizontal and one vertical backstroke start handgrip and currently swimmers can adopt different starting variants. The start performance is related to the exertion of maximal force in the shortest time, as other high-velocity movements; thus, the study of the current variants in-between them from a neuromuscular standpoint is indispensable for training support. The use of different handgrips did not affect upper and lower limb electromyographic activity; angular kinematics and overall 15 m backstroke start profile. Independent of the start variant selected, the role played by each upper and lower limb muscles at different starting phases should be considered in specific resistance training program to optimize backstroke start performance. PMID:26336346

  14. Neuromuscular Activity of Upper and Lower Limbs during two Backstroke Swimming Start Variants.

    PubMed

    De Jesus, Karla; De Jesus, Kelly; Medeiros, Alexandre I A; Gonçalves, Pedro; Figueiredo, Pedro; Fernandes, Ricardo J; Vilas-Boas, João Paulo

    2015-09-01

    swimmers' vertex reaches the 15 m mark) is decisive in short distance events.In 2008, FINA approved the Omega OSB11 starting block (Swiss Timing Ltd., Switzerland) with two horizontal and one vertical backstroke start handgrip and currently swimmers can adopt different starting variants.The start performance is related to the exertion of maximal force in the shortest time, as other high-velocity movements; thus, the study of the current variants in-between them from a neuromuscular standpoint is indispensable for training support.The use of different handgrips did not affect upper and lower limb electromyographic activity; angular kinematics and overall 15 m backstroke start profile.Independent of the start variant selected, the role played by each upper and lower limb muscles at different starting phases should be considered in specific resistance training program to optimize backstroke start performance. PMID:26336346

  15. Effects of Short- and Long-Duration Space Flight on Neuromuscular Function

    NASA Technical Reports Server (NTRS)

    Buxton, Roxanne E.; Spiering, Barry A.; Ryder, Jeffrey W.; Ploutz-Snyder, Lori L.; Bloomberg, Jacob J.

    2010-01-01

    The Functional Task Tests (FTT) is an interdisciplinary study designed to correlate the changes in functional tasks (such as emergency egress, ladder climbing, and hatch opening) with changes in neuromuscular, cardiovascular, and sensorimotor function. One aspect of the FTT, the neuromuscular function test, is used to investigate the neuromuscular component underlying changes in the ability of astronauts to perform functional tasks (representative of critical mission tasks) safely and quickly after flight. PURPOSE: To describe neuromuscular function after short- and long-duration space flight. METHODS: To date, 5 crewmembers on short-duration (10- to 15-day) missions and 3 on long-duration missions have participated. Crewmembers were assessed 30 days before flight, on landing day (short-duration subjects only) and 1, 6, and 30 days after landing. The interpolated twitch technique, which utilizes a combination of maximal voluntary contractions and electrically evoked contractions, was used to assess the maximal voluntary isometric force (MIF) and central activation capacity of the knee extensors. Leg-press and bench-press devices were used to assess MIF and maximal dynamic power of the lower and upper body respectively. Specifically, power was measured during concentric-only ballistic throws of the leg-press sled and bench-press bar loaded to 40% and 30% of MIF respectively. RESULTS: Data are currently being collected from both Shuttle and ISS crewmembers. Emerging data indicate that measures of knee extensor muscle function are decreased with long-duration flight. DISCUSSION: The relationships between flight duration, neural drive, and muscle performance are of particular interest. Ongoing research will add to the current sample size and will focus on defining changes in muscle performance measures after long-duration space flight.

  16. Comparative investigation of the pharmacology of fish and mammalian neuromuscular systems

    SciTech Connect

    Gant, D.B.

    1985-01-01

    Neuromuscular pharmacology has been extensively studied in mammals but there have been few investigations examining the neuromuscular systems of fish. In situ experiments have shown that the basic cholinergic characteristics of fish neuromuscular junctions are different from those of mammals. In order to further understand the nature of these differences, the nicotinic acetylcholine receptors (AChR) of rat and buffalo sculpin (Enophrys bison) neuromuscular junctions and the AChR of electric ray (Torpedo california) electroplax, were investigated using receptor binding analysis. A rapid filtration assay was utilized to measure (/sup 125/I)..cap alpha..-BGT binding to tissue membranes. Scatchard analysis of (/sup 175/I)..cap alpha..-BGT binding was performed on sculpin pectoral muscle rat gastrocnemius, rat denervated gastrocnemius, and Torpedo electroplax. The affinity constant was similar for all tissues studied. In competition studies, d-tubocurarine had the highest affinity for the (/sup 125/I)-..cap alpha..-BGT binding site in all tissues, illustrating the nicotinic nature of the binding sites. Acetylcholine had high affinity for the rat gastrocnemius binding site and low affinity for the sculpin pectoral muscle and Torpedo electroplax binding site. Atropine had high affinity for the sculpin pectoral muscle binding site when compared to the rate gastrocnemius and Torpedo electroplax binding site, indicating that the sculpin pectoral site may have some mixed muscarinic-nicitinic characteristics. These results indicate that there are definite qualitative as well as quantitative differences between the fish skeletal muscle nicotinic receptor and the nicotinic receptor of fish electroplax and rat skeletal muscle.

  17. Effects of in vivo injury on the neuromuscular junction in healthy and dystrophic muscles

    PubMed Central

    Pratt, Stephen JP; Shah, Sameer B; Ward, Christopher W; Inacio, Mario P; Stains, Joseph P; Lovering, Richard M

    2013-01-01

    The most common and severe form of muscular dystrophy is Duchenne muscular dystrophy (DMD), a disorder caused by the absence of dystrophin, a structural protein found on the cytoplasmic surface of the sarcolemma of striated muscle fibres. Considerable attention has been dedicated to studying myofibre damage and muscle plasticity, but there is little information to determine if damage from contraction-induced injury occurs at or near the nerve terminal axon. We used α-bungarotoxin to compare neuromuscular junction (NMJ) morphology in healthy (wild-type, WT) and dystrophic (mdx) mouse quadriceps muscles and evaluated transcript levels of the post-synaptic muscle-specific kinase signalling complex. Our focus was to study changes in NMJs after injury induced with an established in vivo animal injury model. Neuromuscular transmission, electromyography (EMG), and NMJ morphology were assessed 24 h after injury. In non-injured muscle, muscle-specific kinase expression was significantly decreased in mdx compared to WT. Injury resulted in a significant loss of maximal torque in WT (39 ± 6%) and mdx (76 ± 8%) quadriceps, but significant changes in NMJ morphology, neuromuscular transmission and EMG data were found only in mdx following injury. Compared with WT mice, motor end-plates of mdx mice demonstrated less continuous morphology, more disperse acetylcholine receptor aggregates and increased number of individual acetylcholine receptor clusters, an effect that was exacerbated following injury. Neuromuscular transmission failure increased and the EMG measures decreased after injury in mdx mice only. The data show that eccentric contraction-induced injury causes morphological and functional changes to the NMJs in mdx skeletal muscle, which may play a role in excitation–contraction coupling failure and progression of the dystrophic process. PMID:23109110

  18. Physiologic neuromuscular dental paradigm for the diagnosis and treatment of temporomandibular disorders.

    PubMed

    Raman, Prabu

    2014-08-01

    Shifting from traditional anatomical/mechanistic models, the physiologic neuromuscular dentistry (PNMD) paradigm acknowledges the primacy of physiology in shaping and controlling anatomy in a functioning human body. Occlusal disharmony from mandibular discrepancy to cranium leads to temporomandibular disorders (TMD), which is a disease of musculoskeletal imbalance in the postural chain exceeding the individual's physiologic adaptive capacity. To diagnose optimal craniomandibular alignment, PNMD is guided by real-time objective physiologic data such as electromyography (EMG). PMID:25174214

  19. Characterization of neuromuscular synapse function abnormalities in multiple Duchenne muscular dystrophy mouse models.

    PubMed

    van der Pijl, Elizabeth M; van Putten, Maaike; Niks, Erik H; Verschuuren, Jan J G M; Aartsma-Rus, Annemieke; Plomp, Jaap J

    2016-06-01

    Duchenne muscular dystrophy (DMD) is an X-linked myopathy caused by dystrophin deficiency. Dystrophin is present intracellularly at the sarcolemma, connecting actin to the dystrophin-associated glycoprotein complex. Interestingly, it is enriched postsynaptically at the neuromuscular junction (NMJ), but its synaptic function is largely unknown. Utrophin, a dystrophin homologue, is also concentrated at the NMJ, and upregulated in DMD. It is possible that the absence of dystrophin at NMJs in DMD causes neuromuscular transmission defects that aggravate muscle weakness. We studied NMJ function in mdx mice (lacking dystrophin) and wild type mice. In addition, mdx/utrn(+/-) and mdx/utrn(-/-) mice (lacking utrophin) were used to investigate influences of utrophin levels. The three Duchenne mouse models showed muscle weakness when comparatively tested in vivo, with mdx/utrn(-/-) mice being weakest. Ex vivo muscle contraction and electrophysiological studies showed a reduced safety factor of neuromuscular transmission in all models. NMJs had ~ 40% smaller miniature endplate potential amplitudes compared with wild type, indicating postsynaptic sensitivity loss for the neurotransmitter acetylcholine. However, nerve stimulation-evoked endplate potential amplitudes were unchanged. Consequently, quantal content (i.e. the number of acetylcholine quanta released per nerve impulse) was considerably increased. Such a homeostatic compensatory increase in neurotransmitter release is also found at NMJs in myasthenia gravis, where autoantibodies reduce acetylcholine receptors. However, high-rate nerve stimulation induced exaggerated endplate potential rundown. Study of NMJ morphology showed that fragmentation of acetylcholine receptor clusters occurred in all models, being most severe in mdx/utrn(-/-) mice. Overall, we showed mild 'myasthenia-like' neuromuscular synaptic dysfunction in several Duchenne mouse models, which possibly affects muscle weakness and degeneration. PMID:27037492

  20. The adrenergic-neurone blocking action of some coumaran compounds

    PubMed Central

    Fielden, R.; Roe, A. M.; Willey, G. L.

    1964-01-01

    Ethyldimethyl(7-methylcoumaran-3-yl)ammonium iodide (SK&F 90,109) and its guanidine analogue [N-(7-methylcoumaran-3-yl)guanidine nitrate] (SK&F 90,238) abolish the effects of adrenergic nerve stimulation in cats, as do xylocholine and bretylium. SK&F 90,109 has slight sympathomimetic actions; these are less marked than in SK&F 90,238. Large doses of SK&F 90,109 have an action, dependent on local noradrenaline stores, that delays the appearance of adrenergic-neurone blockade in conscious cats. Responses to adrenaline are, in general, enhanced by each drug, but SK&F 90,238 transiently antagonizes tachycardia induced by adrenaline and isoprenaline. Both drugs inhibit the release of noradrenaline from the spleen during splenic nerve stimulation, but the release of catechol amines from the adrenal glands, in response to electrical or chemical stimulation, is unimpaired. In contrast to the prolonged adrenergic-neurone blocking action, any inhibition of the effects of cholinergic nerve stimulation is transient. Large intravenous doses produce neuromuscular blockade. The compounds have a slight central depressant action. In contrast to reserpine and guanethidine the noradrenaline content of rat hearts is not appreciably lowered 24 hr after a single dose of either drug. Unlike xylocholine they are not local anaesthetics. Related compounds also block the effects of adrenergic-nerve stimulation. The possible modes of action of these drugs are discussed. PMID:14256809

  1. Loss of glial neurofascin155 delays developmental synapse elimination at the neuromuscular junction.

    PubMed

    Roche, Sarah L; Sherman, Diane L; Dissanayake, Kosala; Soucy, Geneviève; Desmazieres, Anne; Lamont, Douglas J; Peles, Elior; Julien, Jean-Pierre; Wishart, Thomas M; Ribchester, Richard R; Brophy, Peter J; Gillingwater, Thomas H

    2014-09-17

    Postnatal synapse elimination plays a critical role in sculpting and refining neural connectivity throughout the central and peripheral nervous systems, including the removal of supernumerary axonal inputs from neuromuscular junctions (NMJs). Here, we reveal a novel and important role for myelinating glia in regulating synapse elimination at the mouse NMJ, where loss of a single glial cell protein, the glial isoform of neurofascin (Nfasc155), was sufficient to disrupt postnatal remodeling of synaptic circuitry. Neuromuscular synapses were formed normally in mice lacking Nfasc155, including the establishment of robust neuromuscular synaptic transmission. However, loss of Nfasc155 was sufficient to cause a robust delay in postnatal synapse elimination at the NMJ across all muscle groups examined. Nfasc155 regulated neuronal remodeling independently of its canonical role in forming paranodal axo-glial junctions, as synapse elimination occurred normally in mice lacking the axonal paranodal protein Caspr. Rather, high-resolution proteomic screens revealed that loss of Nfasc155 from glial cells was sufficient to disrupt neuronal cytoskeletal organization and trafficking pathways, resulting in reduced levels of neurofilament light (NF-L) protein in distal axons and motor nerve terminals. Mice lacking NF-L recapitulated the delayed synapse elimination phenotype observed in mice lacking Nfasc155, suggesting that glial cells regulate synapse elimination, at least in part, through modulation of the axonal cytoskeleton. Together, our study reveals a glial cell-dependent pathway regulating the sculpting of neuronal connectivity and synaptic circuitry in the peripheral nervous system. PMID:25232125

  2. Optimization of force in the Wingate Test for children with a neuromuscular disease.

    PubMed

    Van Mil, E; Schoeber, N; Calvert, R E; Bar-or, O

    1996-09-01

    Determination of the optimal braking force (Fopt in the Wingate Anaerobic Test (WAnT) among healthy people has been determined based on total body mass. The abnormal muscle mass to total body mass ratio in individuals with neuromuscular disabilities invalidates this approach. This study was intended to validate the optimal force obtained from the Force Velocity Test (FVT) and from an estimate of lean arm volume as two alternative predictors for the Fopt. Twenty-eight 6- to 16-yr-old girls and boys with neuromuscular diseases performed the arm WAnT six times (three trials in each of two visits) against various braking forces to directly determine Fopt. They also performed the arm Force Velocity Test to assess optimal force (FoptFVT). Lean arm volume was determined by anthropometry (ALV) and water displacement (WLV). Correlations between Fopt on the one hand, and FoptFVT, WLV, and ALV on the other, were: R2 = 0.91, 0.81, and 0.82, respectively. Total body mass was the worst predictor (R2 = 0.65). Thus, Fopt obtained from either FVT or lean arm volume estimate is a useful predictor of the Fopt for mean power of the WAnT in children and adolescents with a neuromuscular disability. PMID:8882994

  3. Physiological control of elaborate male courtship: Female choice for neuromuscular systems

    PubMed Central

    Fusani, Leonida; Barske, Julia; Day, Lainy D.; Fuxjager, Matthew J.; Schlinger, Barney A.

    2015-01-01

    Males of many animal species perform specialized courtship behaviours to gain copulations with females. Identifying physiological and anatomical specializations underlying performance of these behaviours helps clarify mechanisms through which sexual selection promotes the evolution of elaborate courtship. Our knowledge about neuromuscular specializations that support elaborate displays is limited to a few model species. In this review, we focus on the physiological control of the courtship of a tropical bird, the golden-collared manakin, which has been the focus of our research for nearly 20 years. Male manakins perform physically elaborate courtship displays that are quick, accurate and powerful. Females seem to choose males based on their motor skills suggesting that neuromuscular specializations possessed by these males are driven by female choice. Male courtship is activated by androgens and androgen receptors are expressed in qualitatively and quantitatively unconventional ways in manakin brain, spinal cord and skeletal muscles. We propose that in some species, females select males based on their neuromuscular capabilities and acquired skills and that elaborate steroid-dependent courtship displays evolve to signal these traits. PMID:25086380

  4. The Drosophila wings apart gene anchors a novel, evolutionarily conserved pathway of neuromuscular development.

    PubMed

    Morriss, Ginny R; Jaramillo, Carmelita T; Mikolajczak, Crystal M; Duong, Sandy; Jaramillo, Maryann S; Cripps, Richard M

    2013-11-01

    wings apart (wap) is a recessive, semilethal gene located on the X chromosome in Drosophila melanogaster, which is required for normal wing-vein patterning. We show that the wap mutation also results in loss of the adult jump muscle. We use complementation mapping and gene-specific RNA interference to localize the wap locus to the proximal X chromosome. We identify the annotated gene CG14614 as the gene affected by the wap mutation, since one wap allele contains a non-sense mutation in CG14614, and a genomic fragment containing only CG14614 rescues the jump-muscle phenotypes of two wap mutant alleles. The wap gene lies centromere-proximal to touch-insensitive larva B and centromere-distal to CG14619, which is tentatively assigned as the gene affected in introverted mutants. In mutant wap animals, founder cell precursors for the jump muscle are specified early in development, but are later lost. Through tissue-specific knockdowns, we demonstrate that wap function is required in both the musculature and the nervous system for normal jump-muscle formation. wap/CG14614 is homologous to vertebrate wdr68, DDB1 and CUL4 associated factor 7, which also are expressed in neuromuscular tissues. Thus, our findings provide insight into mechanisms of neuromuscular development in higher animals and facilitate the understanding of neuromuscular diseases that may result from mis-expression of muscle-specific or neuron-specific genes. PMID:24026097

  5. Cardiorespiratory, neuromuscular and kinematic responses to stationary running performed in water and on dry land.

    PubMed

    Alberton, Cristine Lima; Cadore, Eduardo Lusa; Pinto, Stephanie Santana; Tartaruga, Marcus Peikriszwili; da Silva, Eduardo Marczwski; Kruel, Luiz Fernando Martins

    2011-06-01

    The purpose of this study was to analyze the cardiorespiratory, neuromuscular and kinematic responses obtained during the stationary running in aquatic and dry land environments. Twelve women took part in the experimental protocol. Stationary running was performed for 4 min at three submaximal cadences and for 15 s at maximal velocity, with the collection of kinematic (peak hip angular velocity (AV)), cardiorespiratory (oxygen uptake (VO(2))) and neuromuscular variables (electromyographic (EMG) signal from the rectus femoris (RF), vastus lateralis (VL), semitendinosus (ST) and short head of the biceps femoris (BF) muscles) in land-based and water-based test protocols. Factorial ANOVA was used, with an alpha level of 0.05. AV was significantly higher when the exercise was performed on land, and became significantly higher as the execution cadence increased. Similarly, VO(2) was significantly higher in the land-based exercise and rose as cadence increased. With the increase in the submaximal execution cadences, there was no corresponding increase in the EMG signal from the VL, BF, RF and ST muscles in either environment, though such a significantly increase was seen between the submaximal cadences and the maximal velocity. Dry land presented significantly greater EMG signal responses for all muscles at the submaximal cadences, except for the ST muscle. However, at the maximal velocity, all the analyzed muscle groups showed similar responses in both environments. In summary, for both environments, cardiorespiratory responses can be maximized by increasing the submaximal cadences, while neuromuscular responses are only optimized by using maximal velocity. PMID:21127897

  6. Cardiorespiratory and neuromuscular responses during water aerobics exercise performed with and without equipment.

    PubMed

    Pinto, S S; Cadore, E L; Alberton, C L; Silva, E M; Kanitz, A C; Tartaruga, M P; Kruel, L F M

    2011-12-01

    The aim of the study was to compare the cardiorespiratory and neuromuscular responses to water aerobics exercise performed with and without equipment. 15 women performed stationary jogging combined with elbow flexion/extension without equipment, with water-drag forces equipment and with water-floating equipment, at 2 submaximal cadences and at maximal cadence. Heart rate, oxygen uptake and electromyographic signal from biceps brachii, triceps brachii, biceps femoris and rectus femoris were collected during the exercise. The heart rate and oxygen uptake showed significantly higher values during the execution of the water aerobics exercise with either equipment compared to the execution without equipment. In addition, significant difference was found between submaximal cadences. For neuromuscular responses, no significant differences were found between the submaximal cadences for all muscles analyzed; however, significant differences were found between these submaximal cadences and the maximal cadence. Similarly, the results showed no significant differences between the execution of the exercise with or without equipment, except in the muscle activation of triceps brachii and biceps femoris, which was higher when using water-floating and water-drag forces equipment, respectively. In conclusion, the water aerobics exercise presented higher cardiorespiratory responses with equipment and also increased the cadence of execution. Nevertheless, neuromuscular responses were higher only at maximal cadence. PMID:22052026

  7. Laminin-database v.2.0: an update on laminins in health and neuromuscular disorders

    PubMed Central

    Golbert, Daiane C. F.; Santana-van-Vliet, Eliane; Mundstein, Alex S.; Calfo, Vicente; Savino, Wilson; de Vasconcelos, Ana Tereza R.

    2014-01-01

    The laminin (LM)-database, hosted at http://www.lm.lncc.br, was published in the NAR database 2011 edition. It was the first database that provided comprehensive information concerning a non-collagenous family of extracellular matrix proteins, the LMs. In its first version, this database contained a large amount of information concerning LMs related to health and disease, with particular emphasis on the haemopoietic system. Users can easily access several tabs for LMs and LM-related molecules, as well as LM nomenclatures and direct links to PubMed. The LM-database version 2.0 integrates data from several publications to achieve a more comprehensive knowledge of LMs in health and disease. The novel features include the addition of two new tabs, ‘Neuromuscular Disorders’ and ‘miRNA-–LM Relationship’. More specifically, in this updated version, an expanding set of data has been displayed concerning the role of LMs in neuromuscular and neurodegenerative diseases, as well as the putative involvement of microRNAs. Given the importance of LMs in several biological processes, such as cell adhesion, proliferation, differentiation, migration and cell death, this upgraded version expands for users a panoply of information, regarding complex molecular circuitries that involve LMs in health and disease, including neuromuscular and neurodegenerative disorders. PMID:24106090

  8. Quantitative neuromuscular ultrasound in intensive care unit-acquired weakness: A systematic review.

    PubMed

    Bunnell, Aaron; Ney, John; Gellhorn, Alfred; Hough, Catherine L

    2015-11-01

    Intensive care unit-acquired weakness (ICU-AW) causes significant morbidity and impairment in critically ill patients. Recent advances in neuromuscular ultrasound (NMUS) allow evaluation of neuromuscular pathology early in critical illness. Here we review application of ultrasound in ICU-AW. MEDLINE-indexed articles were searched for terms relevant to ultrasound and critical illness. Two reviewers evaluated the resulting abstracts (n = 218) and completed full-text review (n = 13). Twelve studies and 1 case report were included. Ten studies evaluated muscle thickness or cross-sectional area (CSA): 8 reported a decrease, and 2 reported no change. Two studies reported preservation of muscle thickness in response to neuromuscular electrical stimulation, and 1 found no preservation. One study found decreases in gray-scale standard deviation, but no change in echogenicity. One study described increases in echogenicity and fasciculations. Ultrasound reliability in ICU-AW is not fully established. Further investigation is needed to identify ultrasound measures that reliably predict clinical, electrodiagnostic, and pathologic findings of ICU-AW. PMID:26044880

  9. Requirement of enhanced Survival Motoneuron protein imposed during neuromuscular junction maturation

    PubMed Central

    Kariya, Shingo; Obis, Teresa; Garone, Caterina; Akay, Turgay; Sera, Fusako; Iwata, Shinichi; Homma, Shunichi; Monani, Umrao R.

    2014-01-01

    Spinal muscular atrophy is a common motor neuron disease caused by low survival motoneuron (SMN), a key protein in the proper splicing of genes. Restoring the protein is therefore a promising therapeutic strategy. Implementation of this strategy, however, depends on defining the temporal requirements for SMN. Here, we used controlled knockdown of SMN in transgenic mice to determine the precise postnatal stage requirements for this protein. Reducing SMN in neonatal mice resulted in a classic SMA-like phenotype. Unexpectedly, depletion of SMN in adults had relatively little effect. Insensitivity to low SMN emerged abruptly at postnatal day 17, which coincided with establishment of the fully mature neuromuscular junction (NMJ). Mature animals depleted of SMN eventually exhibited evidence of selective neuromuscular pathology that was made worse by traumatic injury. The ability to regenerate the mature NMJ in aged or injured SMN-depleted mice was grossly impaired, a likely consequence of the inability to meet the surge in demand for motoneuronal SMN that was seen in controls. Our results demonstrate that relative maturity of the NMJ determines the temporal requirement for the SMN protein. These observations suggest that the use of potent but potentially deleterious SMN-enhancing agents could be tapered in human patients once the neuromuscular system matures and reintroduced as needed to enhance SMN for remodeling aged or injured NMJs. PMID:24463453

  10. Purinergic neuromuscular transmission in the gastrointestinal tract; functional basis for future clinical and pharmacological studies

    PubMed Central

    Jiménez, Marcel; Clavé, Pere; Accarino, Anna; Gallego, Diana

    2014-01-01

    Nerve-mediated relaxation is necessary for the correct accomplishment of gastrointestinal (GI) motility. In the GI tract, NO and a purine are probably released by the same inhibitory motor neuron as inhibitory co-transmitters. The P2Y1 receptor has been recently identified as the receptor responsible for purinergic smooth muscle hyperpolarization and relaxation in the human gut. This finding has been confirmed in P2Y1-deficient mice where purinergic neurotransmission is absent and transit time impaired. However, the mechanisms responsible for nerve-mediated relaxation, including the identification of the purinergic neurotransmitter(s) itself, are still debatable. Possibly different mechanisms of nerve-mediated relaxation are present in the GI tract. Functional demonstration of purinergic neuromuscular transmission has not been correlated with structural studies. Labelling of purinergic neurons is still experimental and is not performed in routine pathology studies from human samples, even when possible neuromuscular impairment is suspected. Accordingly, the contribution of purinergic neurotransmission in neuromuscular diseases affecting GI motility is not known. In this review, we have focused on the physiological mechanisms responsible for nerve-mediated purinergic relaxation providing the functional basis for possible future clinical and pharmacological studies on GI motility targeting purine receptors. PMID:24910216

  11. Loss of Glial Neurofascin155 Delays Developmental Synapse Elimination at the Neuromuscular Junction

    PubMed Central

    Roche, Sarah L.; Sherman, Diane L.; Dissanayake, Kosala; Soucy, Geneviève; Desmazieres, Anne; Lamont, Douglas J.; Peles, Elior; Julien, Jean-Pierre; Wishart, Thomas M.; Ribchester, Richard R.; Brophy, Peter J.

    2014-01-01

    Postnatal synapse elimination plays a critical role in sculpting and refining neural connectivity throughout the central and peripheral nervous systems, including the removal of supernumerary axonal inputs from neuromuscular junctions (NMJs). Here, we reveal a novel and important role for myelinating glia in regulating synapse elimination at the mouse NMJ, where loss of a single glial cell protein, the glial isoform of neurofascin (Nfasc155), was sufficient to disrupt postnatal remodeling of synaptic circuitry. Neuromuscular synapses were formed normally in mice lacking Nfasc155, including the establishment of robust neuromuscular synaptic transmission. However, loss of Nfasc155 was sufficient to cause a robust delay in postnatal synapse elimination at the NMJ across all muscle groups examined. Nfasc155 regulated neuronal remodeling independently of its canonical role in forming paranodal axo–glial junctions, as synapse elimination occurred normally in mice lacking the axonal paranodal protein Caspr. Rather, high-resolution proteomic screens revealed that loss of Nfasc155 from glial cells was sufficient to disrupt neuronal cytoskeletal organization and trafficking pathways, resulting in reduced levels of neurofilament light (NF-L) protein in distal axons and motor nerve terminals. Mice lacking NF-L recapitulated the delayed synapse elimination phenotype observed in mice lacking Nfasc155, suggesting that glial cells regulate synapse elimination, at least in part, through modulation of the axonal cytoskeleton. Together, our study reveals a glial cell-dependent pathway regulating the sculpting of neuronal connectivity and synaptic circuitry in the peripheral nervous system. PMID:25232125

  12. Morphological analysis of neuromuscular junction development and degeneration in rodent lumbrical muscles

    PubMed Central

    Sleigh, James N.; Burgess, Robert W.; Gillingwater, Thomas H.; Cader, M. Zameel

    2014-01-01

    Background The neuromuscular junction (NMJ) is a specialised synapse formed between a lower motor neuron and a skeletal muscle fibre, and is an early pathological target in numerous nervous system disorders, including amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth disease (CMT), and spinal muscular atrophy (SMA). Being able to accurately visualize and quantitatively characterise the NMJ in rodent models of neurological conditions, particularly during the early stages of disease, is thus of clear importance. New Method We present a method for dissection of rodent deep lumbrical muscles located in the hind-paw, and describe how to perform immunofluorescent morphological analysis of their NMJs. Results These techniques allow the temporal assessment of a number of developmental and pathological NMJ phenotypes in lumbrical muscles. Comparison with Existing Methods Small muscles, such as the distal hind-limb lumbrical muscles, possess a major advantage over larger muscles, such as gastrocnemius, in that they can be whole-mounted and the entire innervation pattern visualised. This reduces preparation time and ambiguity when evaluating important neuromuscular phenotypes. Conclusions Together, these methods will allow the reader to perform a detailed and accurate analysis of the neuromuscular system in rodent models of disease in order to identify pertinent features of neuropathology. PMID:24530702

  13. Comparing targeted exome and whole exome approaches for genetic diagnosis of neuromuscular disorders

    PubMed Central

    Gorokhova, Svetlana; Cerino, Mathieu; Mathieu, Yves; Courrier, Sébastien; Desvignes, Jean-Pierre; Salgado, David; Béroud, Christophe; Krahn, Martin; Bartoli, Marc

    2015-01-01

    Massively parallel sequencing is rapidly becoming a widely used method in genetic diagnostics. However, there is still no clear consensus as to which approach can most efficiently identify the pathogenic mutations carried by a given patient, while avoiding false negative and false positive results. We developed a targeted exome approach (MyoPanel2) in order to optimize genetic diagnosis of neuromuscular disorders. Using this approach, we were able to analyse 306 genes known to be mutated in myopathies as well as in related disorders, obtaining 98.8% target sequence coverage at 20 ×. Moreover, MyoPanel2 was able to detect 99.7% of 11,467 known mutations responsible for neuromuscular disorders. We have then used several quality control parameters to compare performance of the targeted exome approach with that of whole exome sequencing. The results of this pilot study of 140 DNA samples suggest that targeted exome sequencing approach is an efficient genetic diagnostic test for most neuromuscular diseases. PMID:27054082

  14. Role of extracellular matrix proteins and their receptors in the development of the vertebrate neuromuscular junction.

    PubMed

    Singhal, Neha; Martin, Paul T

    2011-11-01

    The vertebrate neuromuscular junction (NMJ) remains the best-studied model for understanding the mechanisms involved in synaptogenesis, due to its relatively large size, its simplicity of patterning, and its unparalleled experimental accessibility. During neuromuscular development, each skeletal myofiber secretes and deposits around its extracellular surface an assemblage of extracellular matrix (ECM) proteins that ultimately form a basal lamina. This is also the case at the NMJ, where the motor nerve contributes additional factors. Before most of the current molecular components were known, it was clear that the synaptic ECM of adult skeletal muscles was unique in composition and contained factors sufficient to induce the differentiation of both pre- and postsynaptic membranes. Biochemical, genetic, and microscopy studies have confirmed that agrin, laminin (221, 421, and 521), collagen IV (α3-α6), collagen XIII, perlecan, and the ColQ-bound form of acetylcholinesterase are all synaptic ECM proteins with important roles in neuromuscular development. The roles of their many potential receptors and/or binding proteins have been more difficult to assess at the genetic level due to the complexity of membrane interactions with these large proteins, but roles for MuSK-LRP4 in agrin signaling and for integrins, dystroglycan, and voltage-gated calcium channels in laminin-dependent phenotypes have been identified. Synaptic ECM proteins and their receptors are involved in almost all aspects of synaptic development, including synaptic initiation, topography, ultrastructure, maturation, stability, and transmission. PMID:21766463

  15. The Knockdown of αkap Alters the Postsynaptic Apparatus of Neuromuscular Junctions in Living Mice

    PubMed Central

    Martinez-Pena y Valenzuela, Isabel; Aittaleb, Mohamed; Chen, Po-Ju

    2015-01-01

    A muscle-specific nonkinase anchoring protein (αkap), encoded within the calcium/calmodulin kinase II (camk2) α gene, was recently found to control the stability of acetylcholine receptor (AChR) clusters on the surface of cultured myotubes. However, it remains unknown whether this protein has any effect on receptor stability and the maintenance of the structural integrity of neuromuscular synapses in vivo. By knocking down the endogenous expression of αkap in mouse sternomastoid muscles with shRNA, we found that the postsynaptic receptor density was dramatically reduced, the turnover rate of receptors at synaptic sites was significantly increased, and the insertion rates of both newly synthesized and recycled receptors into the postsynaptic membrane were depressed. Moreover, we found that αkap shRNA knockdown impaired synaptic structure as postsynaptic AChR clusters and their associated postsynaptic scaffold proteins within the neuromuscular junction were completely eliminated. These results provide new mechanistic insight into the role of αkap in regulating the stability of the postsynaptic apparatus of neuromuscular synapses. PMID:25834039

  16. Telemedicine system for the care of patients with neuromuscular disease and chronic respiratory failure

    PubMed Central

    Morete, Emilio; González, Francisco

    2014-01-01

    Introduction Neuromuscular diseases cause a number of limitations which may be improved by using a telemedicine system. These include functional impairment and dependence associated with muscle weakness, the insidious development of respiratory failure and episodes of exacerbation. Material and methods The present study involved three patients with severe neuromuscular disease, chronic respiratory failure and long-term mechanical ventilation, who were followed up using a telemedicine platform. The telemedicine system is based on videoconferencing and telemonitoring of cardiorespiratory variables (oxygen saturation, heart rate, blood pressure and electrocardiogram). Two different protocols were followed depending on whether the patient condition was stable or unstable. Results Over a period of 5 years, we analyzed a series of variables including use of the system, patient satisfaction and clinical impact. Overall we performed 290 videoconference sessions, 269 short monitoring oximetry measurements and 110 blood pressure measurements. With respect to the clinical impact, after enrolment in the telemedicine program, the total number of hospital admissions fell from 18 to 3. Conclusions Our findings indicate that the system was user friendly for patients and care givers. Patient satisfaction scores were acceptable. The telemedicine system was effective for the home treatment of three patients with severe neuromuscular diseases and reduced the need for hospital admissions. PMID:25395959

  17. Minimally Invasive Scoliosis Surgery: A Novel Technique in Patients with Neuromuscular Scoliosis

    PubMed Central

    Sarwahi, Vishal; Amaral, Terry; Wendolowski, Stephen; Gecelter, Rachel; Gambassi, Melanie; Plakas, Christos; Liao, Benita; Kalantre, Sarika; Katyal, Chhavi

    2015-01-01

    Minimally invasive surgery (MIS) has been described in the treatment of adolescent idiopathic scoliosis (AIS) and adult scoliosis. The advantages of this approach include less blood loss, shorter hospital stay, earlier mobilization, less tissue disruption, and relatively less pain. However, despite these significant benefits, MIS approach has not been reported in neuromuscular scoliosis patients. This is possibly due to concerns with longer surgery time, which is further increased due to more levels fused and instrumented, challenges of pelvic fixation, size and number of incisions, and prolonged anesthesia. We modified the MIS approach utilized in our AIS patients to be implemented in our neuromuscular patients. Our technique allows easy passage of contoured rods, placement of pedicle screws without image guidance, partial/complete facet resection, and all standard reduction maneuvers. Operative time needed to complete this surgery is comparable to the standard procedure and the majority of our patients have been extubated at the end of procedure, spending 1 day in the PICU and 5-6 days in the hospital. We feel that MIS is not only a feasible but also a superior option in patients with neuromuscular scoliosis. Long-term results are unavailable; however, short-term results have shown multiple benefits of this approach and fewer limitations. PMID:26649305

  18. Laminin-database v.2.0: an update on laminins in health and neuromuscular disorders.

    PubMed

    Golbert, Daiane C F; Santana-van-Vliet, Eliane; Mundstein, Alex S; Calfo, Vicente; Savino, Wilson; de Vasconcelos, Ana Tereza R

    2014-01-01

    The laminin (LM)-database, hosted at http://www.lm.lncc.br, was published in the NAR database 2011 edition. It was the first database that provided comprehensive information concerning a non-collagenous family of extracellular matrix proteins, the LMs. In its first version, this database contained a large amount of information concerning LMs related to health and disease, with particular emphasis on the haemopoietic system. Users can easily access several tabs for LMs and LM-related molecules, as well as LM nomenclatures and direct links to PubMed. The LM-database version 2.0 integrates data from several publications to achieve a more comprehensive knowledge of LMs in health and disease. The novel features include the addition of two new tabs, 'Neuromuscular Disorders' and 'miRNA--LM Relationship'. More specifically, in this updated version, an expanding set of data has been displayed concerning the role of LMs in neuromuscular and neurodegenerative diseases, as well as the putative involvement of microRNAs. Given the importance of LMs in several biological processes, such as cell adhesion, proliferation, differentiation, migration and cell death, this upgraded version expands for users a panoply of information, regarding complex molecular circuitries that involve LMs in health and disease, including neuromuscular and neurodegenerative disorders. PMID:24106090

  19. Effects of apamin, quinine and neuromuscular blockers on calcium-activated potassium channels in guinea-pig hepatocytes.

    PubMed Central

    Cook, N S; Haylett, D G

    1985-01-01

    The bee venom peptide, apamin, has been radiolabelled with 125I, the monoiodinated derivative purified, and its binding to intact guinea-pig liver cells studied. At 37 degrees C 125I-monoiodoapamin associated with, and dissociated from, guinea-pig hepatocytes remarkably rapidly. The association and dissociation rate constants were 1.4 X 10(8) M-1 s-1 and 0.035 s-1 respectively. Equilibrium binding studies demonstrated a saturable binding component compatible with 1:1 binding to a single class of site and having an equilibrium dissociation constant (KL) of 390 pM. The maximal binding capacity was 1.1 fmol mg-1 dry wt. of tissue. Unlabelled apamin displaced bound 125I-monoiodoapamin with a KI of 380 pM, which is consistent with the concentration of apamin required to inhibit Ca2+-activated K+ permeability (PK(Ca) ) in these cells. Inhibitable binding of 125I-monoiodoapamin to rat hepatocytes was much less than to guinea-pig hepatocytes and could not be reliably quantified. Neither was there any discernible inhibitable binding to human erythrocytes. This is in keeping with the reported lack of apamin-sensitive Ca2+-activated K+ channels in these cell types. Various agents were tested for their ability to inhibit monoiodoapamin binding to, and Ca2+-mediated K+ efflux from, guinea-pig hepatocytes. All compounds tested which inhibited binding also blocked K+ efflux at similar concentrations. TEA and quinine affected hepatocytes only at high concentration (KI = 5.8 and 0.51 mM respectively). 9-aminoacridine, quinacrine and chloroquine were slightly more effective (KI = 70-180 microM). By far the most active compounds (apart from apamin) were the neuromuscular blocking agents; tubocurarine, pancuronium and atracurium (KI = 7.5, 6.8 and 4.5 microM respectively). Gallamine was slightly less effective (KI = 14 microM) and decamethonium and hexamethonium much less so (KI = 620 and 760 microM respectively). 3,4-diaminopyridine, alpha-bungarotoxin and tetrodotoxin were among

  20. Importin-β11 Regulates Synaptic pMAD and Thereby Influences Synaptic Development and Function at the Drosophila Neuromuscular Junction

    PubMed Central

    Higashi-Kovtun, Misao E.; Mosca, Timothy J.; Dickman, Dion K.; Meinertzhagen, Ian A.; Schwarz, Thomas L.

    2010-01-01

    Importin proteins act both at the nuclear pore to promote substrate entry and in the cytosol during signal trafficking. Here, we describe mutations in the Drosophila gene importin-β11 which has not previously been analyzed genetically. Mutants of importin-β11 died as late pupae from neuronal defects and neuronal importin-β11 was present not only at nuclear pores but also in the cytosol and at synapses. Neurons lacking importin-β11 were viable and properly differentiated but exhibited discrete defects. Synaptic transmission was defective in adult photoreceptors and at larval neuromuscular junctions. Mutant photoreceptor axons formed grossly normal projections and synaptic terminals in the brain, but synaptic arbors on larval muscles were smaller while still containing appropriate synaptic components. BMP signaling was the apparent cause of the observed NMJ defects. Importin-β11 interacted genetically with the BMP pathway and at mutant synaptic boutons, a key component of this pathway, phosphorylated Mothers Against Decapentaplegic (pMAD), was reduced. Neuronal expression of an importin-β11 transgene rescued this phenotype as well as the other observed neuromuscular phenotypes. Despite the loss of synaptic pMAD, pMAD persisted in motor neuron nuclei, suggesting a specific impairment in the local function of pMAD. Restoring levels of pMAD to mutant terminals via expression of constitutively active type I BMP receptors or by reducing retrograde transport in motor neurons, also restored synaptic strength and morphology. Thus, importin-β11 function interacts with the BMP pathway to regulate a pool of pMAD that must be present at the presynapse for its proper development and function. PMID:20392948

  1. NCCN Evidence Blocks.

    PubMed

    Carlson, Robert W; Jonasch, Eric

    2016-05-01

    NCCN has developed a series of Evidence Blocks: graphics that provide ratings for each recommended treatment regimen in terms of efficacy, toxicity, quality and consistency of the supporting data, and affordability. The NCCN Evidence Blocks are currently available in 10 tumor types within the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). At a glance, patients and providers can understand how a given treatment was assessed by the NCCN Guidelines Panel and get a sense of how a given treatment may match individual needs and preferences. Robert W. Carlson, MD, CEO of NCCN, described the reasoning behind this new feature and how the tool is used, and Eric Jonasch, MD, Professor of Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center, and Vice Chair of the NCCN Kidney Cancer Panel, described its applicability in the management of metastatic renal cell carcinoma. PMID:27226499

  2. Neuromuscular Evaluation With Single-Leg Squat Test at 6 Months After Anterior Cruciate Ligament Reconstruction

    PubMed Central

    Hall, Michael P.; Paik, Ronald S.; Ware, Anthony J.; Mohr, Karen J.; Limpisvasti, Orr

    2015-01-01

    Background: Criteria for return to unrestricted activity after anterior cruciate ligament (ACL) reconstruction varies, with some using time after surgery as the sole criterion—most often at 6 months. Patients may have residual neuromuscular deficits, which may increase the risk of ACL injury. A single-leg squat test (SLST) can dynamically assess for many of these deficits prior to return to unrestricted activity. Hypothesis: A significant number of patients will continue to exhibit neuromuscular deficits with SLST at 6 months after ACL reconstruction. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients using a standardized accelerated rehabilitation protocol at their 6-month follow-up after primary ACL reconstruction were enrolled. Evaluation included bilateral SLST, single-leg hop distance, hip abduction strength, and the subjective International Knee Documentation Committee (IKDC) score. Results: Thirty-three patients were enrolled. Poor performance of the operative leg SLST was found in 15 of 33 patients (45%). Of those 15 patients, 7 (45%) had concomitant poor performance of the nonoperative leg compared with 2 of 18 patients (11%) in those who demonstrated good performance in the operative leg. The poor performers were significantly older (33.6 years) than the good performers (24.2 years) (P = .007). Those with poor performance demonstrated decreased hip abduction strength (17.6 kg operative leg vs 20.5 kg nonoperative leg) (P = .024), decreased single-leg hop distance (83.3 cm operative leg vs 112.3 cm nonoperative leg) (P = .036), and lower IKDC scores (67.9 vs 82.3) (P = .001). Conclusion: Nearly half of patients demonstrated persistent neuromuscular deficits on SLST at 6 months, which is when many patients return to unrestricted activity. Those with poor performance were of a significantly older age, decreased hip abduction strength, decreased single-leg hop distance, and lower IKDC subjective scores. Clinical Relevance: The SLST

  3. Caffeine Ingestion Reverses the Circadian Rhythm Effects on Neuromuscular Performance in Highly Resistance-Trained Men

    PubMed Central

    Mora-Rodríguez, Ricardo; Pallarés, Jesús García; López-Samanes, Álvaro; Ortega, Juan Fernando; Fernández-Elías, Valentín E.

    2012-01-01

    Purpose To investigate whether caffeine ingestion counteracts the morning reduction in neuromuscular performance associated with the circadian rhythm pattern. Methods Twelve highly resistance-trained men underwent a battery of neuromuscular tests under three different conditions; i) morning (10:00 a.m.) with caffeine ingestion (i.e., 3 mg kg−1; AMCAFF trial); ii) morning (10:00 a.m.) with placebo ingestion (AMPLAC trial); and iii) afternoon (18:00 p.m.) with placebo ingestion (PMPLAC trial). A randomized, double-blind, crossover, placebo controlled experimental design was used, with all subjects serving as their own controls. The neuromuscular test battery consisted in the measurement of bar displacement velocity during free-weight full-squat (SQ) and bench press (BP) exercises against loads that elicit maximum strength (75% 1RM load) and muscle power adaptations (1 m s−1 load). Isometric maximum voluntary contraction (MVCLEG) and isometric electrically evoked strength of the right knee (EVOKLEG) were measured to identify caffeine's action mechanisms. Steroid hormone levels (serum testosterone, cortisol and growth hormone) were evaluated at the beginning of each trial (PRE). In addition, plasma norepinephrine (NE) and epinephrine were measured PRE and at the end of each trial following a standardized intense (85% 1RM) 6 repetitions bout of SQ (POST). Results In the PMPLAC trial, dynamic muscle strength and power output were significantly enhanced compared with AMPLAC treatment (3.0%–7.5%; p≤0.05). During AMCAFF trial, muscle strength and power output increased above AMPLAC levels (4.6%–5.7%; p≤0.05) except for BP velocity with 1 m s−1 load (p = 0.06). During AMCAFF, EVOKLEG and NE (a surrogate of maximal muscle sympathetic nerve activation) were increased above AMPLAC trial (14.6% and 96.8% respectively; p≤0.05). Conclusions These results indicate that caffeine ingestion reverses the morning neuromuscular declines in highly resistance

  4. Intraocular radiation blocking

    SciTech Connect

    Finger, P.T.; Ho, T.K.; Fastenberg, D.M.; Hyman, R.A.; Stroh, E.M.; Packer, S.; Perry, H.D. )

    1990-09-01

    Iodine-based liquid radiographic contrast agents were placed in normal and tumor-bearing (Greene strain) rabbit eyes to evaluate their ability to block iodine-125 radiation. This experiment required the procedures of tumor implantation, vitrectomy, air-fluid exchange, and 125I plaque and thermoluminescent dosimetry (TLD) chip implantation. The authors quantified the amount of radiation attenuation provided by intraocularly placed contrast agents with in vivo dosimetry. After intraocular insertion of a blocking agent or sham blocker (saline) insertion, episcleral 125I plaques were placed across the eye from episcleral TLD dosimeters. This showed that radiation attenuation occurred after blocker insertion compared with the saline controls. Then computed tomographic imaging techniques were used to describe the relatively rapid transit time of the aqueous-based iohexol compared with the slow transit time of the oil-like iophendylate. Lastly, seven nontumor-bearing eyes were primarily examined for blocking agent-related ocular toxicity. Although it was noted that iophendylate induced intraocular inflammation and retinal degeneration, all iohexol-treated eyes were similar to the control eyes at 7 and 31 days of follow-up. Although our study suggests that intraocular radiopaque materials can be used to shield normal ocular structures during 125I plaque irradiation, a mechanism to keep these materials from exiting the eye must be devised before clinical application.

  5. Block 3. This photograph depicts the northern view of Block ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Block 3. This photograph depicts the northern view of Block 2 towards the May D & F Tower from the main path along the western facades - Skyline Park, 1500-1800 Arapaho Street, Denver, Denver County, CO

  6. Channel blocking of MspA revisited.

    PubMed

    Perera, Ayomi S; Wang, Hongwang; Basel, Matthew T; Pokhrel, Megh Raj; Gamage, Pubudu Siyambalagoda; Kalita, Mausam; Wendel, Sebastian; Sears, Bryan; Welideniya, Dhanushi; Liu, Yao; Turro, Claudia; Troyer, Deryl L; Bossmann, Stefan H

    2013-01-01

    Porin A from Mycobacterium smegmatis (MspA) is a highly stable, octameric channel protein, which acts as the main transporter of electrolytes across the cell membrane. MspA features a narrow, negatively charged constriction zone, allowing stable binding of various analytes thereby blocking the channel. Investigation of channel blocking of mycobacterial porins is of significance in developing alternate treatment methods for tuberculosis. The concept that ruthenium(II)quaterpyridinium complexes have the capability to act as efficient channel blockers for MspA and related porins, emerged after very high binding constants were measured by high-performance liquid chromatography and steady-state luminescence studies. Consequently, the interactions between the ruthenium(II) complex RuC2 molecules and MspA, leading to RuC2@MspA assemblies, have been studied utilizing time-resolved absorption/emission, atomic force microscopy, dynamic light scattering, ζ potential measurements, and isothermal titration calorimetry. The results obtained provide evidence for the formation of clusters/large aggregates of RuC2 and MspA. The results are of interest with respect to utilizing prospective channel blockers in porins. The combination of results from conceptually different techniques shed some light onto the chemical nature of MspA-channel blocker interactions thus contributing to the development of a paradigm for channel blocking. PMID:23214433

  7. 31 CFR 510.301 - Blocked account; blocked property.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Blocked account; blocked property. 510.301 Section 510.301 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY NORTH KOREA SANCTIONS REGULATIONS General Definitions § 510.301 Blocked...

  8. View southeast of caps for blocks for JFK; blocks are ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View southeast of caps for blocks for JFK; blocks are used to support ship when it is repositioned to paint inaccessible areas masked by original support blocks. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Carpentry Shop, League Island, Philadelphia, Philadelphia County, PA

  9. Block Copolymer Templates for Optical Materials and Devices

    NASA Astrophysics Data System (ADS)

    Urbas, Augustine; Martin, Maldovan; Carter, W. C.; Thomas, E. L.; Fasolka, Michael; Fraser, Cassandra

    2002-03-01

    Block copolymers can act as super-lattices for creating novel optical structures. We have fabricated block copolymer photonic crystals from one, two and three dimensionally periodic systems and have enhanced their dielectric properties towards creating complete 3D band gaps. By using carefully selected blends of linear and star block copolymers, we are able to create hierarchical blends which exhibit precise molecular positioning of fluorescent molecules. We are exploring these unique patterning capabilities of block copolymer systems for the formation of ordered arrays of optically active components within a photonic crystal. Precise location of both fluorescent and nonlinear components within block copolymer photonic crystals affords new opportunities for creating low threshold, upconverting and array lasers as well as optical modulators and other photonic devices.

  10. Blocking Interleukin-1 in Rheumatic Diseases

    PubMed Central

    Goldbach-Mansky, Raphaela

    2011-01-01

    The role of the potent proinflammatory cytokine IL-1 in disease could clinically be investigated with the development of the IL-1 blocking agent anakinra (Kineret®), a recombinant IL-1 receptor antagonist. It was first tested in patients with sepsis without much benefit but was later FDA approved for the treatment of patients with rheumatoid arthritis. More recently IL-1 blocking therapies are used successfully to treat a new group of immune-mediated inflammatory conditions, autoinflammatory diseases. These conditions include rare hereditary fever syndromes and pediatric and adult conditions of Still’s disease. Recently the FDA approved two additional longer acting IL-1 blocking agents, for the treatment of cryopyrin-associated periodic syndromes (CAPS), an IL-1 dependent autoinflammatory syndrome. The study of autoinflammatory diseases revealed mechanisms of IL-1 mediated organ damage and provided concepts to a better understanding of the pathogenesis of more common diseases such as gout and Type 2 diabetes which show initial promising results with IL-1 blocking therapy. PMID:20074280

  11. On the asymptotic distribution of block-modified random matrices

    NASA Astrophysics Data System (ADS)

    Arizmendi, Octavio; Nechita, Ion; Vargas, Carlos

    2016-01-01

    We study random matrices acting on tensor product spaces which have been transformed by a linear block operation. Using operator-valued free probability theory, under some mild assumptions on the linear map acting on the blocks, we compute the asymptotic eigenvalue distribution of the modified matrices in terms of the initial asymptotic distribution. Moreover, using recent results on operator-valued subordination, we present an algorithm that computes, numerically but in full generality, the limiting eigenvalue distribution of the modified matrices. Our analytical results cover many cases of interest in quantum information theory: we unify some known results and we obtain new distributions and various generalizations.

  12. Act resilient.

    PubMed

    Joseph, Genie; Bice-Stephens, Wynona

    2014-01-01

    Attendees have reported changing from being fearful to serene, from listless to energized, from disengaged to connected, and becoming markedly less anxious in a few weeks. Anecdotally, self-reported stress levels have been reduced by over 50% after just one class. Attendees learn not to be afraid of their feelings by working with emotions in a playful manner. When a person can act angry, but separate himself from his personal story, the emotional energy exists in a separate form that is not attached to specific events, and can be more easily dealt with and neutralized. Attendees are taught to "take out the emotional trash" through expressive comedy. They become less intimated by their own emotional intensity and triggers as they learn how even metaphorical buckets of anger, shame, guilt and hurt can be emotionally emptied. The added benefit is that this is accomplished without the disclosure of personal information of the requirement to reexperience past pain which can trigger its own cascade of stress. PMID:24706248

  13. Ear - blocked at high altitudes

    MedlinePlus

    High altitudes and blocked ears; Flying and blocked ears; Eustachian tube dysfunction - high altitude ... you are going up or coming down from high altitudes. Chewing gum the entire time you are changing ...

  14. Porous block nanofiber composite filters

    DOEpatents

    Ginley, David S.; Curtis, Calvin J.; Miedaner, Alexander; Weiss, Alan J.; Paddock, Arnold

    2016-08-09

    Porous block nano-fiber composite (110), a filtration system (10) and methods of using the same are disclosed. An exemplary porous block nano-fiber composite (110) includes a porous block (100) having one or more pores (200). The porous block nano-fiber composite (110) also includes a plurality of inorganic nano-fibers (211) formed within at least one of the pores (200).

  15. Using Attribute Blocks with Children

    ERIC Educational Resources Information Center

    Huntsberger, John P.

    1978-01-01

    The classroom use of attribute blocks to develop thinking skills is defended in this article. Divergent-productive thinking is identified as an important skill that can be developed by using these blocks. However, teacher commitment and involvement in the program is considered necessary. Suggestions for using these blocks are included. (MA)

  16. Building Curriculum during Block Play

    ERIC Educational Resources Information Center

    Andrews, Nicole

    2015-01-01

    Blocks are not just for play! In this article, Nicole Andrews describes observing the interactions of three young boys enthusiastically engaged in the kindergarten block center of their classroom, using blocks in a building project that displayed their ability to use critical thinking skills, physics exploration, and the development of language…

  17. Property Blocks: Games and Activities.

    ERIC Educational Resources Information Center

    Humphreys, Alan, Ed.; Dailey, Jean, Ed.

    This pamphlet describes the property blocks produced by MINNEMAST, and discusses their use in the development of thinking processes. Classification systems, including block diagrams and tree diagrams, are discussed. Sixteen classroom activities and eleven games which use the blocks are described. Suggestions to the teacher for further reading are…

  18. Biomechanical and neuromuscular characteristics of male athletes: implications for the development of anterior cruciate ligament injury prevention programs.

    PubMed

    Sugimoto, Dai; Alentorn-Geli, Eduard; Mendiguchía, Jurdan; Samuelsson, Kristian; Karlsson, Jon; Myer, Gregory D

    2015-06-01

    Prevention of anterior cruciate ligament (ACL) injury is likely the most effective strategy to reduce undesired health consequences including reconstruction surgery, long-term rehabilitation, and pre-mature osteoarthritis occurrence. A thorough understanding of mechanisms and risk factors of ACL injury is crucial to develop effective prevention programs, especially for biomechanical and neuromuscular modifiable risk factors. Historically, the available evidence regarding ACL risk factors has mainly involved female athletes or has compared male and female athletes without an intra-group comparison for male athletes. Therefore, the principal purpose of this article was to review existing evidence regarding the investigation of biomechanical and neuromuscular characteristics that may imply aberrant knee kinematics and kinetics that would place the male athlete at risk of ACL injury. Biomechanical evidence related to knee kinematics and kinetics was reviewed by different planes (sagittal and frontal/coronal), tasks (single-leg landing and cutting), situation (anticipated and unanticipated), foot positioning, playing surface, and fatigued status. Neuromuscular evidence potentially related to ACL injury was reviewed. Recommendations for prevention programs for ACL injuries in male athletes were developed based on the synthesis of the biomechanical and neuromuscular characteristics. The recommendations suggest performing exercises with multi-plane biomechanical components including single-leg maneuvers in dynamic movements, reaction to and decision making in unexpected situations, appropriate foot positioning, and consideration of playing surface condition, as well as enhancing neuromuscular aspects such as fatigue, proprioception, muscle activation, and inter-joint coordination. PMID:25663251

  19. The postsynaptic submembrane machinery at the neuromuscular junction: requirement for rapsyn and the utrophin/dystrophin-associated complex.

    PubMed

    Banks, Glen B; Fuhrer, Christian; Adams, Marvin E; Froehner, Stanley C

    2003-01-01

    Neuromuscular synapse formation is brought about by a complex bi-directional exchange of information between the innervating motor neuron and its target skeletal muscle fiber. Agrin, a heparin sulfate proteoglycan, is released from the motor nerve terminal to activate its muscle-specific kinase (MuSK) receptor that leads to a second messenger cascade requiring rapsyn to ultimately bring about AChR clustering in the muscle membrane. Rapsyn performs many functions in skeletal muscle. First, rapsyn and AChRs co-target to the postsynatic apparatus. Second, rapsyn may self associate to stabilize and promote AChR clustering. Third, rapsyn is essential for AChR cluster formation. Fourth, rapsyn is required to transduce the agrin-evoked MuSK phosphorylation signal to AChRs. Finally, rapsyn links AChRs to the utrophin-associated complex, which appears to be required for AChR stabilization as well as maturation of the neuromuscular junction. Proteins within the utrophin-associated complex such as alpha-dystrobrevin and alpha-syntrophin are also important for signaling events that affect neuromuscular synapse stability and function. Here we review our current understanding of the role of the postsynaptic-submembrane machinery involving rapsyn and the utrophin-associated complex at the neuromuscular synapse. In addition we briefly review how these studies of the neuromuscular junction relate to GABAergic and glycinergic synapses in the CNS. PMID:15034263

  20. CORE SATURATION BLOCKING OSCILLATOR

    DOEpatents

    Spinrad, R.J.

    1961-10-17

    A blocking oscillator which relies on core saturation regulation to control the output pulse width is described. In this arrangement an external magnetic loop is provided in which a saturable portion forms the core of a feedback transformer used with the thermionic or semi-conductor active element. A first stationary magnetic loop establishes a level of flux through the saturation portion of the loop. A second adjustable magnet moves the flux level to select a saturation point giving the desired output pulse width. (AEC)